bluuebunny/crossref_metadata_2025 huggingface dataset:
The case for low carbohydrate diets in diabetes management
Authors: Arora Surender K , McFarlane Samy I
Published: July 2005

A low fat, high carbohydrate diet in combination with regular exercise is the traditional recommendation for treating diabetes. Compliance with these lifestyle modifications is less than satisfactory, however, and a high carbohydrate diet raises postprandial plasma glucose and insulin secretion, thereby increasing risk of CVD, hypertension, dyslipidemia, obesity and diabetes. Moreover, the current epidemic of diabetes and obesity has been, over the past three decades, accompanied by a significant decrease in fat consumption and an increase in carbohydrate consumption. This apparent failure of the traditional diet, from a public health point of view, indicates that alternative dietary approaches are needed. Because carbohydrate is the major secretagogue of insulin, some form of carbohydrate restriction is a prima facie candidate for dietary control of diabetes. Evidence from various randomized controlled trials in recent years has convinced us that such diets are safe and effective, at least in short-term. These data show low carbohydrate diets to be comparable or better than traditional low fat high carbohydrate diets for weight reduction, improvement in the dyslipidemia of diabetes and metabolic syndrome as well as control of blood pressure, postprandial glycemia and insulin secretion. Furthermore, the ability of low carbohydrate diets to reduce triglycerides and to increase HDL is of particular importance. Resistance to such strategies has been due, in part, to equating it with the popular Atkins diet. However, there are many variations and room for individual physician planning. Some form of low carbohydrate diet, in combination with exercise, is a viable option for patients with diabetes. However, the extreme reduction of carbohydrate of popular diets (<30 g/day) cannot be recommended for a diabetic population at this time without further study. On the other hand, the dire objections continually raised in the literature appear to have very little scientific basis. Whereas it is traditional to say that more work needs to be done, the same is true of the assumed standard low fat diets which have an ambiguous record at best. We see current trends in the national dietary recommendations as a positive sign and an appropriate move in the right direction.
Case report: severe heat stroke with multiple organ dysfunction – a novel intravascular treatment approach
Authors: Broessner Gregor , Beer Ronny , Franz Gerhard , Lackner Peter , Engelhardt Klaus , Brenneis Christian , Pfausler Bettina , Schmutzhard Erich
Published: July 2005

Introduction

We report the case of a patient who developed a severe post-exertional heat stroke with consecutive multiple organ dysfunction resistant to conventional antipyretic treatment, necessitating the use of a novel endovascular device to combat hyperthermia and maintain normothermia.

Methods

A 38-year-old male suffering from severe heat stroke with predominant signs and symptoms of encephalopathy requiring acute admission to an intensive care unit, was admitted to a ten-bed neurological intensive care unit of a tertiary care hospital. The patient developed consecutive multiple organ dysfunction with rhabdomyolysis, and hepatic and respiratory failure. Temperature elevation was resistant to conventional treatment measures. Aggressive intensive care treatment included forced diuresis and endovascular cooling to combat hyperthermia and maintain normothermia.

Results

Analyses of serum revealed elevation of proinflammatory cytokines (TNF alpha, IL-6), cytokines (IL-2R), anti-inflammatory cytokines (IL-4) and chemokines (IL-8) as well as signs of rhabdomyolysis and hepatic failure. Aggressive intensive care treatment as forced diuresis and endovascular cooling (CoolGard® and CoolLine®) to combat hyperthermia and maintain normothermia were used successfully to treat this severe heat stroke.

Conclusion

In this case of severe heat stroke, presenting with multiple organ dysfunction and elevation of cytokines and chemokines, which was resistant to conventional cooling therapies, endovascular cooling may have contributed significantly to the reduction of body temperature and, possibly, avoided a fatal result.
Genomic mapping of RNA polymerase II reveals sites of co-transcriptional regulation in human cells
Authors: Brodsky Alexander S , Meyer Clifford A , Swinburne Ian A , Hall Giles , Keenan Benjamin J , Liu Xiaole S , Fox Edward A , Silver Pamela A
Published: July 2005

Background

Transcription by RNA polymerase II is regulated at many steps including initiation, promoter release, elongation and termination. Accumulation of RNA polymerase II at particular locations across genes can be indicative of sites of regulation. RNA polymerase II is thought to accumulate at the promoter and at sites of co-transcriptional alternative splicing where the rate of RNA synthesis slows.

Results

To further understand transcriptional regulation at a global level, we determined the distribution of RNA polymerase II within regions of the human genome designated by the ENCODE project. Hypophosphorylated RNA polymerase II localizes almost exclusively to 5' ends of genes. On the other hand, localization of total RNA polymerase II reveals a variety of distinct landscapes across many genes with 74% of the observed enriched locations at exons. RNA polymerase II accumulates at many annotated constitutively spliced exons, but is biased for alternatively spliced exons. Finally, RNA polymerase II is also observed at locations not in gene regions.

Conclusion

Localizing RNA polymerase II across many millions of base pairs in the human genome identifies novel sites of transcription and provides insights into the regulation of transcription elongation. These data indicate that RNA polymerase II accumulates most often at exons during transcription. Thus, a major factor of transcription elongation control in mammalian cells is the coordination of transcription and pre-mRNA processing to define exons.
Standards update on perfusion equipment and practice
Authors: Kurusz Mark
Published: July 2005

Standards applying to the manufacture, testing and labeling of perfusion components and equipment, as well as those dealing with clinical use of extracorporeal circulation, have been promulgated by both standards-setting organizations and professional organizations. The rationale and purpose for device standards are discussed, and many organizations and the processes involved in developing standards are described. Perfusion checklists used during equipment set-up, use and at termination have a long track record of acceptance by clinicians. Evolving techniques have prompted revisions to the basic perfusion checklist, which should be considered a guide for development of institution-specific checklists. Current and future work by international standards-setting organizations is described.
Perfusion safety in Europe: managing risks, learning from mistakes
Authors: Graves K
Published: July 2005

There is a renewed effort in Europe to develop strategies for improving patient safety in hospital care. Nevertheless, traditional hierarchical structures, methods of teaching, and the established tendency to focus on human error rather than organisational causes in medical accidents prohibit effective problem analysis and subsequent learning from our mistakes. Changing the work environment in order to enhance safety in cardiovascular perfusion services requires new efforts in individual clinics, in national perfusion societies, and on a European level.

What tools do we have at hand in our profession to alter these influences and to improve perfusion safety? How can national perfusion societies in Europe enhance improvements which extend outside national boundaries?
A blame-free culture in the NHS: quixotic notion or achievable ambition?
Authors: Lilleyman John
Published: July 2005

The National Patient Safety Agency aims to generate an open and fair culture in the NHS where errors and near misses are reported, studied and learnt from. Safety rests in the design of equipment, systems, procedures, buildings and corporate frameworks, together with awareness of the human factors behind slips, lapses, mistakes and violations and how to anticipate and control them. Cultural shift can only be achieved if staff are willing to report and learn from such events and from near misses. It is a long way from the current widespread climate of blame and cover-up, but the change has begun.
Sterility validity period of vials after multiple sampling under vertical laminar airflow hood
Authors: De Giorgi I , Sadeghipour F , Favet J , Bonnabry P
Published: July 2005

Study objectives. The aim of this study is to validate the sterility period of vials after multiple sampling under Grade A vertical laminar airflow hood.

Methods. Vials filled aseptically with a sterile culture medium have been sampled with syringes three times a week over one month under Grade A vertical laminar airflow hood and in the meanwhile, keeping the vials out of the laminar airflow hoods.

Results. No microbial growth has been observed. On the basis of these results, it has been decided to modify our standard operating procedures, to allow keeping the vials for two weeks in a box out of the laminar airflow hoods (ambient temperature Grade B) or any controlled environment (under refrigeration).

Conclusions. This study validates the multiple use of vials of small to large volumes (5-100 mL), to simplify handling and to reduce the costs in centralized cytostatic reconstitution units in hospital pharmacies, with no microbial risk.
A reporting system for the assessment of chemotherapy toxicity
Authors: Sassi Graziella , Striano Barbara , Merlo Ugo A
Published: July 2005

Purpose. Toxicity may distress patients and cause delay or a discontinuance of scheduled chemotherapies. A key issue is to create a reporting system in order to assess toxicities and also evaluate treatments.

Methods. In the Oncology Unit 3000 intravenous chemotherapies are administered each year, mostly in the day hospital. In summer 2002, oncologists and pharmacists agreed to assess myelosuppression and gastrointestinal toxicity of grades 3 and 4. Pharmacists designed a form and a database in order to collect toxicity data for every patient. The oncologist records type and grade of toxicity (according to the NCI CTC) on the patient chart before chemotherapy commences. During the validation of computerized prescriptions the pharmacist collects data about possible toxicities of every grade.

Results. From August-October 2002, 675 chemotherapies were administered. Seventy-two patients developed GI toxicity at various grades, nine of grade 3 and two of grade 4. Regimens with fluorouracil, carboplatin, cisplatin and oxaliplatin were highly involved in GI toxicity. Eighty-seven patients developed myelosuppression, two of grade 3 and 33 of grade 4. Regimens with epirubicin, cyclophosphamide, paclitaxel, cisplatin and carboplatin were highly involved in myelosuppression. After the first report, oncologists and pharmacists decided to stop collecting data in order to improve the reporting system and to plan regular meetings.

Conclusions. A reliable reporting system is a valuable tool for oncologists to manage toxicity and to evaluate chemotherapy regimens. Assessing chemotherapy toxicity is a good opportunity for pharmacists to take part in preventing toxicity and reducing patient’s discomfort.
Depression, the Perimenopause, and Estrogen Therapy
Authors: SCHMIDT PETER J.
Published: July 2005

Abstract: The focus of this chapter is the relationship between the onset of depression in women and the reproductive events of the perimenopause. The perimenopause is a time of considerable variability in reproductive function, which appears in some women to be associated with an increased susceptibility to depression. Elevated gonadotropin levels occur during the late perimenopause, with plasma follicle‐stimulating hormone levels increasing in association with impaired ovarian function and decreased estradiol secretion. It is unclear, however, whether the variability in ovarian hormone secretion during the perimenopause has a substantial causal role in the development of depression. Epidemiologic studies have documented that most women do not become depressed during the menopausal transition. However, recent longitudinal studies suggest that in some women, perimenopause‐related reproductive events play a role in the onset of depression. Additionally, randomized controlled trials have documented the short‐term (3‐6 weeks) antidepressant efficacy of estradiol in depressed perimenopausal women. Thus, although depression is not a uniform accompaniment of the menopausal transition, in some women age‐related changes in ovarian estrogen production may alter central nervous system function and predispose them to develop depression.
Is the Estrogen Controversy Over? Deconstructing the Women's Health Initiative Study: A Critical Evaluation of the Evidence
Authors: HARMAN S.MITCHELL , NAFTOLIN FREDERICK , BRINTON ELIOT A. , JUDELSON DEBRA R.
Published: July 2005

Abstract: The Women's Health Initiative (WHI) hormone trials have been widely interpreted as demonstrating that combined menopausal hormone therapy (HT) fails to protect against—and may increase—cardiovascular disease (CVD), stroke, and dementia in menopausal women, regardless of whether initiated early in the menopause or later. This conclusion does not agree with results of large epidemiological studies showing protection by HT and by estrogen replacement alone (ET) against CVD and dementia. One possible reason for this inconsistency is that the epidemiologic data are confounded by “healthy user bias.” Another possible explanation is that most women in the observational studies initiated ET or HT at or near the menopausal transition, at which point there is little or no arterial injury, whereas, in the WHI studies, older women, averaging approximately 12 years postmenopausal, many of whom would have had significant asymptomatic atherosclerosis, were treated. Substantial data demonstrate atheropreventive effects of estrogen before vascular damage occurs, whereas adverse effects of oral estrogen on thrombosis and inflammation may predominate once complex atheromas are present. Similarly, the excess of dementia observed in older WHI women treated with oral conjugated estrogen could be due to cerebral thromboses (multi‐infarct dementia). Given the uncertain relevance of the WHI (and other published randomized clinical trials) to initiation of HT in perimenopausal women, and its subsequent continuation for atheroprevention, new trials will be needed to resolve whether early intervention with estrogen may prevent CVD and/or dementia. The Kronos Early Estrogen Prevention Study (KEEPS), which began in mid‐2005, is a randomized, controlled multicenter trial of HT in recently menopausal women. It will examine surrogate end points as well as risk factors for atherosclerosis.
Estrogen: A Neuroprotective or Proinflammatory Hormone? Emerging Evidence from Reproductive Aging Models
Authors: SOHRABJI FARIDA
Published: July 2005

Abstract: Estrogen or hormone (estrogen + progestin) replacement is typically prescribed to women for relief from vasomotor symptoms at menopause. Observational studies have shown that such replacement also decreases the risk for Alzheimer's disease. Experimental data from a variety of animal models also suggest that estrogen replacement given to ovariectomized animals is largely neuroprotective. However, the recent intervention trial (Women's Health Initiative Memory Study; WHIMS) concluded that estrogen replacement and hormone replacement prescribed to postmenopausal women increased the risk for global cognitive impairment and dementia, respectively. This paper will examine evidence that the disparity in the human and animal data can be reconciled by consideration of the “reproductive” age of the individual receiving estrogen or hormone replacement. Our recent studies comparing the effects of estrogen replacement on young adult animals with those of estrogen replacement to reproductive senescent animals suggest that the estrogen replacement is beneficial when given to “surgically menopausal” (ovariectomized) animals. However, estrogen replacement appears to be deleterious to acyclic reproductive senescent animals, where target organs such as the brain have been in a prolonged estrogen‐deficient state. The paper will also review aging and reproductive age‐related changes in the estrogen receptor (ER) systems, specifically ER‐α, as a potential mechanism for estrogen's deleterious effects in the reproductive senescent animal.
Clinical Pharmacology and Differential Cognitive Efficacy of Estrogen Preparations
Authors: GLEASON CAREY E. , CARLSSON CYNTHIA M. , JOHNSON STERLING , ATWOOD CRAIG , ASTHANA SANJAY
Published: July 2005

Abstract: Menopause is associated with a significant decline in levels of estrogen, which reportedly leads to several distressing symptoms and adverse health effects on various target tissues including those on bones, heart, and brain. Although effective, the long‐term safety and feasibility of therapy with both unopposed and opposed oral conjugated equine estrogen has been questioned by the recent findings of both the Women's Health Initiative (WHI) and the Women's Health Initiative Memory Study (WHIMS). The findings of both these studies have raised several critical issues related to hormone therapy that need to be systematically evaluated in clinical studies. Specifically, these issues relate to the differential efficacy and adverse‐effects profile of various forms of estrogen and progestins, the importance of the route of administration of estrogen, the best timing to initiate postmenopausal hormone therapy, and the efficacy of cyclic versus continuous hormone therapy. This article focuses on estrogen and discusses issues related to selecting the best form and route of administration of the hormone. It includes information on basic clinical pharmacology of various forms of estrogen, neuroendocrinology of the menopause, neurobiology of estradiol and estrone, and results of selected basic science and human intervention studies with relevance to identifying the best form and route of administration of estrogen.
Mechanisms of Progesterone‐Induced Neuroprotection
Authors: SINGH MEHARVAN
Published: July 2005

Abstract: Gonadal steroid hormones such as estrogen and progesterone can no longer be considered strictly within the confines of reproductive function, and with respect to their anatomic targets, extrahypothalamic structures within the brain such as the cerebral cortex have revealed themselves to be important targets. As such, it may come as no surprise that the decline in such hormones, which occurs after the menopause or ovariectomy, can result in neuronal dysfunction. Although estrogen has been shown to help restore the deficits consequent to ovariectomy, it is important to consider that ovariectomy, like the menopause, results in the precipitous loss of not only estrogen but of progesterone as well. As such, the loss of progesterone may contribute to the deficits observed after ovariectomy or the increased risk for Alzheimer's disease seen after the menopause. Indeed, recent evidence supports the neuroprotective potential of progesterone itself. Here, we review the current understanding of some of the diverse mechanisms by which progesterone may reduce neuronal vulnerability to toxic insults relevant to age and age‐associated diseases such as Alzheimer's disease. Further, we comment on the need to carefully consider the various preparations of progestins that are currently available and argue that “not all progestins are created equal,” at least when it comes to influences on neuroprotection and other extrahypothalamic brain functions.
Methodological Issues in Estrogen Treatment Trials for Alzheimer's Disease
Authors: MULNARD RUTH A.
Published: July 2005

Abstract: Over the past two decades, many clinical trials have been conducted using different forms of estrogen therapy with and without progestin supplementation in an effort to treat diagnosed Alzheimer's disease. Design variations among these trials may account for the inconsistent results of these investigations and the persistent gap in knowledge about the appropriate use of estrogen in the treatment paradigm for degenerative diseases.
Estrogens and Cerebrovascular Stroke: What Do Animal Models Teach Us?
Authors: WISE PHYLLIS M.
Published: July 2005

Abstract: Recent findings from the Women's Health Initiative (WHI) suggest that hormone therapy (HT) and estrogen therapy (ET) increase the risk of stroke in postmenopausal women. These results were unexpected based upon many previous clinical, observational, and epidemiological studies and a large body of evidence that come from studies performed in animal models. Before we assume that these results are widely applicable to other hormone preparations and to all older postmenopausal women, we should consider whether the particular hormone preparations, the doses that were used, the age of the women, the length of time that they were postmenopausal prior to the initiation of treatment, and/or their health status may have been important factors in the results of this clinical trial. We believe that results of studies using animal models provide insights into why the result of the WHI should have been expected. Furthermore, results of basic science studies provide a strong rationale for the design of future clinical studies that will more accurately test the effects of ET/HT on the risk and outcomes of cerebrovascular stroke in middle‐aged perimenopausal and early postmenopausal women. We will review data, predominantly from our laboratory, gathered over the past six years that lead us to this conclusion.
Impact of Metabolism on the Safety of Estrogen Therapy
Authors: PROKAI‐TATRAI KATALIN , PROKAI LASZLO
Published: July 2005

Abstract: Estrogen metabolism has received attention owing to the recognition that oxidative metabolism of these hormones could play a very important role in the initiation and evolution of estrogen‐related cancerous processes. This review discusses principal metabolic pathways associated with the molecular constituents found in common hormone formulations. The focus is the formation of catechol estrogens that then oxidize to redox‐active and electrophilic quinones, along with potential mechanisms by which these metabolites contribute to oxidative stress and induce damage to essential biological macromolecules. Recent investigations involving specific estrogen metabolites that may offer potential increase of therapeutic safety for estrogen therapy in the future have also been highlighted.
Estrogen Bows to a New Master: The Role of Gonadotropins in Alzheimer Pathogenesis
Authors: WEBBER KATE M. , CASADESUS GEMMA , MARLATT MICHAEL W. , PERRY GEORGE , HAMLIN CLIVE R. , ATWOOD CRAIG S. , BOWEN RICHARD L. , SMITH MARK A.
Published: July 2005

Abstract: Epidemiological data showing a predisposition of women to develop Alzheimer disease (AD) led many researchers to investigate the role of sex steroids, namely estrogen, in disease pathogenesis. Although there is circumstantial support for the role of estrogen, the unexpected results of the Women's Health Initiative (WHI) Memory Study, which reported an increase in the risk for probable dementia and impaired cognitive performance in postmenopausal women treated with a combination of estrogen and progestin, have raised serious questions regarding the protective effects of estrogen. Although explanations for these surprising results vary greatly, the WHI Memory Study cannot be correctly interpreted without a complete investigation of the effects of the other hormones of the hypothalamic‐pituitary‐gonadal (HPG) axis on the aging brain. Certain hormones of the HPG axis, namely, the gonadotropins (luteinizing hormone and follicle‐stimulating hormone), are not only involved in regulating reproductive function via a complex feedback loop but are also known to cross the blood‐brain barrier. We propose that the increase in gonadotropin concentrations, and not the decrease in steroid hormone (e.g., estrogen) production following menopause/andropause, is a potentially primary causative factor for the development of AD. In this review, we examine how the gonadotropins may play a central and determining role in modulating the susceptibility to, and progression of, AD. On this basis, we suggest that the results of the WHI Memory Study are not only predictable but also avoidable by therapeutically targeting the gonadotropins instead of the sex steroids.
Regulation of the Proapoptotic Factor FOXO1 (FKHR) in Cardiomyocytes by Growth Factors and α1-Adrenergic Agonists
Authors: Morris James B. , Kenney Bronwyn , Huynh Huy , Woodcock Elizabeth A.
Published: July 2005

Apoptotic responses in cardiomyocytes are opposed by the protein kinase Akt (protein kinase B) and thus can be suppressed by a number of growth factors and cytokines. In some cell types, Akt phosphorylates and inactivates members of the forkhead box (FOXO) family of transcription factors that are active in regulating the expression of proapoptotic cytokines and signaling intermediates. In the current study, we investigated the possibility that FOXO1 (FKHR) was expressed, regulated, and functional in cardiomyocytes. Addition of epidermal growth factor (EGF) (10 nm) to neonatal rat cardiomyocytes caused rapid phosphorylation of Akt and slower FOXO1 phosphorylation. In contrast, the α1-adrenergic receptor agonist phenylephrine (50 μm) did not phosphorylate Akt and caused dephosphorylation of FOXO1 acutely and increased FOXO1 expression with chronic exposure. Phenylephrine, but not EGF, caused nuclear translocation of FOXO1, a response that is associated with dephosphorylation. Overexpression of FOXO1 activated transcription of the proapoptotic cytokine, TNFα-related apoptosis-inducing ligand, as indicated by reporter gene activity. This response was enhanced by phenylephrine and inhibited by EGF. FOXO1 is expressed, regulated, and functionally active in cardiomyocytes and thus may contribute to apoptotic responses in heart.
Adenosine 5′-Monophosphate-Activated Protein Kinase Regulates Progesterone Secretion in Rat Granulosa Cells
Authors: Tosca Lucie , Froment Pascal , Solnais Patricia , Ferré Pascal , Foufelle Fabienne , Dupont Joëlle
Published: July 2005

The AMP-activated protein kinase (AMPK) is a major regulator of energy metabolism involved in fatty acid and cholesterol synthesis. In the ovary, cholesterol plays a key role in steroid production. We report the presence of AMPK in rat ovaries, and we have investigated its role in granulosa cells. We show using RT-PCR and Western blot that the mRNAs for the α1/2 and β1/2 subunits and the proteins are found in the ovaries. Immunohistochemistry localized the α1 AMPK subunit in granulosa cells, corpus luteum, and oocyte and less abundantly in theca cells. Treatment with 1 mm 5-amino-imidazole-4-carboxyamide-1-β-d-ribofuranoside (AICAR), an activator of AMPK, increased dose-dependent and time-dependent phosphorylation of AMPKα1 on Thr172 in primary granulosa cells. Simultaneously, phosphorylation of acetyl-coenzyme A carboxylase at Ser79 was also increased. AICAR treatment for 48 h halved progesterone secretion, 3β-HSD protein and mRNA levels, and phosphorylation of both basal MAPK ERK1/2 and p38 and in response to IGF-I and/or FSH in granulosa cells. AICAR treatment (1 mm) had no detectable effect on basal and FSH- and/or IGF-I-induced estradiol production and on granulosa cell proliferation or viability. Adenovirus-mediated expression of dominant negative AMPK totally abolished the effects of AICAR on progesterone secretion, 3β-HSD protein production, and MAPK ERK1/2 and p38 phosphorylation. Moreover, we showed using specific in- hibitors of ERK1/2 and p38 MAPK that the MAPK ERK1/2 and not p38 is involved in progesterone secretion and 3β-HSD expression, strongly suggesting that the activation of AMPK in response to AICAR reduces progesterone production through the MAPK ERK1/2 signaling pathway in rat granulosa cells.
Modulation of Angiogenesis during Adipose Tissue Development in Murine Models of Obesity
Authors: Voros Gabor , Maquoi Erik , Demeulemeester Diego , Clerx Natalie , Collen Désiré , Lijnen H. Roger
Published: July 2005

Development of vasculature and mRNA expression of 17 pro- or antiangiogenic factors were studied during adipose tissue development in nutritionally induced or genetically determined murine obesity models. Subcutaneous (SC) and gonadal (GON) fat pads were harvested from male C57Bl/6 mice kept on standard chow [standard fat diet (SFD)] or on high-fat diet for 0–15 wk and from male ob/ob mice kept on SFD. Ob/ob mice and C57Bl/6 mice on high-fat diet had significantly larger SC and GON fat pads, accompanied by significantly higher blood content, increased total blood vessel volume, and higher number of proliferating cells. mRNA and protein levels of angiopoietin (Ang)-1 were down-regulated, whereas those of thrombospondin-1 were up-regulated in developing adipose tissue in both obesity models. Ang-1 mRNA levels correlated negatively with adipose tissue weight in the early phase of nutritionally induced obesity as well as in genetically determined obesity. Placental growth factor and Ang-2 expression were increased in SC adipose tissue of ob/ob mice, and thrombospondin-2 was increased in both their SC and GON fat pads. mRNA levels of vascular endothelial growth factor (VEGF)-A isoforms VEGF-B, VEGF-C, VEGF receptor-1, -2, and -3, and neuropilin-1 were not markedly modulated by obesity. This modulation of angiogenic factors during development of adipose tissue supports their important functional role in obesity.
α1-Adrenergic Receptor Antagonists: Novel Therapy for Pituitary Adenomas
Authors: Fernando Manory A. , Heaney Anthony P.
Published: July 2005

Pituitary tumors are common and cause considerable morbidity due to local invasion and altered hormone secretion. Doxazosin (dox), a selective α1-adrenergic receptor antagonist, used to treat hypertension, also inhibits prostate cancer cell proliferation. We examined the effects of dox on murine and human pituitary tumor cell proliferation in vitro and in vivo. dox treatment inhibited proliferation of murine pituitary tumor cells, induced G0-G1 cell cycle arrest, and reduced phosphorylated retinoblastoma levels. In addition, increased annexin-fluorescein isothiocyanate immunoreactivity and cleaved caspase-3 levels, in keeping with dox-mediated apoptosis, were observed in the human and murine pituitary tumor cells, and dox administration to mice, harboring corticotroph tumors, decreased tumor growth and reduced plasma ACTH levels. dox-mediated antiproliferative and proapoptotic actions were not confined to α-adrenergic receptor-expressing pituitary tumor cells and were unaffected by cotreatment with the α-adrenergic receptor blocker, phenoxybenzamine. dox treatment led to reduced phosphorylated inhibitory κB (IκB)-α expression, and nuclear factor-κB transcription and decreased basal and TNFα-induced proopiomelanocortin transcriptional activation. These results demonstrate that the selective α1-adrenergic receptor antagonist dox inhibits pituitary tumor cell growth in vitro and in vivo by mechanisms that are in part independent of its α-adrenergic receptor-blocking actions and involve down-regulation of nuclear factor-κB signaling. dox is proposed as a possible novel medical therapy for pituitary tumors.
Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates
Authors: Means Anna L. , Meszoely Ingrid M. , Suzuki Kazufumi , Miyamoto Yoshiharu , Rustgi Anil K. , Coffey Robert J. , Wright Christopher V. E. , Stoffers Doris A. , Leach Steven D.
Published: July 2005

Epithelial metaplasia occurs when one predominant cell type in a tissue is replaced by another, and is frequently associated with an increased risk of subsequent neoplasia. In both mouse and human pancreas, acinar-to-ductal metaplasia has been implicated in the generation of cancer precursors. We show that pancreatic epithelial explants undergo spontaneous acinar-to-ductal metaplasia in response to EGFR signaling, and that this change in epithelial character is associated with the appearance of nestin-positive transitional cells. Lineage tracing involving Cre/lox-mediated genetic cell labeling reveals that acinar-to-ductal metaplasia represents a true transdifferentiation event, mediated by initial dedifferentiation of mature exocrine cells to generate a population of nestin-positive precursors, similar to those observed during early pancreatic development. These results demonstrate that a latent precursor potential resides within mature exocrine cells, and that this potential is regulated by EGF receptor signaling. In addition, these observations provide a novel example of rigorously documented transdifferentiation within mature mammalian epithelium, and suggest that plasticity of mature cell types may play a role in the generation of neoplastic precursors.
Cerebral hypoplasia and craniofacial defects in mice lacking heparan sulfateNdst1gene function
Authors: Grobe Kay , Inatani Masaru , Pallerla Srinivas R. , Castagnola Jan , Yamaguchi Yu , Esko Jeffrey D.
Published: July 2005

Mutant mice bearing a targeted disruption of the heparan sulfate (HS)modifying enzyme GlcNAc N-deacetylase/N-sulfotransferase 1 (Ndst1) exhibit severe developmental defects of the forebrain and forebrain-derived structures, including cerebral hypoplasia, lack of olfactory bulbs, eye defects and axon guidance errors. Neural crest-derived facial structures are also severely affected. We show that properly synthesized heparan sulfate is required for the normal development of the brain and face, and that Ndst1 is a modifier of heparan sulfate-dependent growth factor/morphogen signalling in those tissues. Among the multiple heparan sulfate-binding factors potentially affected in Ndst1 mutant embryos, the facial phenotypes are consistent with impaired sonic hedgehog (Shh) and fibroblast growth factor(Fgf) interaction with mutant heparan sulfate. Most importantly, the data suggest the possibility that defects in heparan sulfate synthesis could give rise to or contribute to a number of developmental brain and facial defects in humans.
Supporting families of critically ill children at home using videoconferencing
Authors: Morgan G J , Grant B , Craig B , Sands A , Casey F
Published: July 2005

Home videoconferencing links for families of children recently discharged with complex congenital heart disease may be useful in monitoring potentially unstable patients. A randomized controlled trial was carried out comparing home videoconferencing with telephone contact. Patients were randomized to an interventional videoconferencing group (n= 14), or to one of two control groups: the first (n = 9) received the same ad hoc telephone support that was available to all patients; the second group (n = 1 3) received regular telephone calls with the same protocol as those in the videoconferencing group. The results from the trial are still being analysed. Our experience with commercial cable modem transmission quickly showed that this is an unsuitable modality. Preliminary results with ISDN videoconferencing are encouraging. Initial results and feedback from families strongly suggest that videoconferencing provides significant benefits over telephone follow-up.
Preferences of general practitioners regarding an application running on a personal digital assistant in acute stroke care
Authors: Veld M H A Huis In't , Van Til J A , Ijzerman M J , Vollenbroek-Hutten M M R
Published: July 2005

An application was developed to optimize information exchange in acute stroke care, with which general practitioners (GPs) could consult hospital emergency units. However, it was difficult to obtain clear preferences from GPs regarding the functional requirements of the information to be transferred or the architecture of the application. Thirteen GPs volunteered to take part in the study. The GPs used a personal digital assistant in their daily work for a period of six weeks when visiting stroke patients during their evening, night and weekend shifts. A conjoint analysis was conducted to obtain the least and most preferred characteristics of the application, to facilitate implementation on a larger scale. The main outcome was that GPs preferred the decision-support facilities and the presence of information about the patient's medical history.
Improved access to subspecialist diabetes care by telemedicine: Cost savings and care measures in the first two years of the FITE diabetes project
Authors: Malasanos Toree H , Burlingame Julie B , Youngblade Lise , Patel Bhavin D , Muir Andrew B
Published: July 2005

We have used telemedicine clinics supplemented by online education to provide effective care for children with diabetes. Before the programme began, the mean interval between visits was 149 days; in year 1 of the programme it was 98 days, and in year 2 it was 89 days. Before the programme, there were on average 1 3 hospitalizations a year (47 days) and this decreased to 3.5 hospitalizations a year (5.5 days). Emergency department visits decreased from 8 to 2.5 per year. On 10 occasions after the programme started, ketosis was managed by telephone intervention alone, relying on family-initiated calls. Over 90% of patients and family members expressed satisfaction with the telemedicine service and wished to continue using it. In all, 95% felt little self-consciousness. Over 90% felt their privacy was respected. The programme saved US$27,860 per year. The present study demonstrated improved access to specialized health care via telemedicine in combination with online education improved health status and reduced costs by reducing hospitalizations and emergency department visits.
Using telemedicine to provide post-discharge support for patients with spinal cord injuries
Authors: Soopramanien Anba , Pain Helen , Stainthorpe Andrew , Menarini Mauro , Ventura Manfredi
Published: July 2005

We are conducting a randomized controlled trial of telemedicine with patients with spinal cord injuries in their own homes. Internet videoconferencing is used at a bandwidth of 128 kbit/s. Data collection began in March 2004. Twelve patients had entered the study by August 2004, but none had completed it. Preliminary results in one case suggest that telemedicine provided various benefits: (1) the patient received advice he would probably not have solicited; (2) it enabled an expert to view the entry site of a pin in the patient's halo brace, to determine whether the general practitioner should be contacted to arrange a swab; (3) it made it easier for the interviewer to understand family interactions during the session. Telemedicine offers an additional tool in the care of geographically widespread outpatients.
Mobile telemetry for pre-hospital thrombolysis: Problems and solutions
Authors: Pedley David K , Beedie Stephen , Ferguson James
Published: July 2005

In the Angus region of Scotland, we have used mobile telemetry to facilitate pre-hospital thrombolysis by paramedic staff. An initial survey demonstrated that connection could be achieved in all but three locations. In the first year of operation, 229 contacts were received. Communication between the ambulance and the base station failed on four occasions (2%). Problems with transmission of an electrocardiogram (ECG) were encountered on 37 occasions (16%). The median time for acquisition and transmission of an ECG was 22 min. This compares with a median time of 59 min for first ECG in a control group from similar locations, who were assessed in hospital. Telemetry offers essential back-up to paramedics adopting a challenging and extended role. Strategies can be developed to deal with signal strength and equipment failure.
Effect of home-based telecardiology on chronic heart failure: Costs and outcomes
Authors: Scalvini S , Capomolla S , Zanelli E , Benigno M , Domenighini D , Paletta L , Glisenti F , Giordano A
Published: July 2005

Chronic heart failure (CHF) remains a common cause of disability. We have investigated the use of home-based telecardiology (HBT) in CHF patients. Four hundred and twenty-six patients were enrolled in the study: 230 in the HBT group and 196 in the usual-care group. HBT consisted of trans-telephonic follow-up and electrocardiogram (ECG) monitoring, followed by visits from the paramedical and medical team. A one-lead ECG recording was transmitted to a receiving station, where a nurse was available for reporting and interactive teleconsultation. The patient could call the centre when assistance was required (tele-assistance), while the team could call the patient for scheduled appointments (telemonitoring). The one-year clinical outcomes showed that there was a significant reduction in rehospitalizations in the HBT group compared with the usual-care group (24% versus 34%, respectively). There was an increase in quality of life in the HBT group (mean Minnesota Living Questionnaire scores 29 and 23.5, respectively). The total costs were lower in the HBT group (107,494 and 140,874, respectively). The results suggest that a telecardiology service can detect and prevent clinical instability, reduce rehospitalization and lower the cost of managing CHF patients.
Telemedicine-assisted home support for patients with advanced chronic obstructive pulmonary disease: Preliminary results after nine-month follow-up
Authors: Vontetsianos Th , Giovas P , Katsaras Th , Rigopoulou A , Mpirmpa G , Giaboudakis P , Koyrelea S , Kontopyrgias G , Tsoulkas B
Published: July 2005

Eighteen well motivated patients with advanced chronic obstructive pulmonary disease, who had had at least four hospitalizations during the previous two years, were included in a home-based telemedicine study. A visiting nurse was equipped with a case containing a laptop computer and a number of medical devices, including an electrocardiogram recorder, spirometer, oximeter and blood pressure monitor. It also contained a videoconference camera, for realtime audiovisual connection with the hospital using the patient's TV set. A single ISDN line (128 kbit/s) was installed in each house before the study began. After nine months, there was a decrease in hospitalizations, emergency department visits and use of health services. The patient's disease knowledge and self-management also improved. It seems likely that adopting telemedicine in everyday clinical practice could substantially improve the care of chronically ill patients.
Mobile phone technology in the management of asthma
Authors: Ryan D , Cobern W , Wheeler J , Price D , Tarassenko L
Published: July 2005

Peak flow monitoring is widely recommended as part of a self-management plan for asthma. We conducted an observational study using electronic peak flow monitoring and mobile phone technology in a UK general practice population over a nine-month period. Patients between 12 and 55 years of age who required treatment with regular inhaled steroids and (as needed) bronchodilators were recruited from nine general practices. Patients were included if their asthma was considered stable (i.e. no exacerbation in the previous three months). No therapeutic intervention was proposed. The primary outcome measure was compliance. In all, 69% of the 46 participants who filled in the post-study questionnaire were ‘satisfied’ or ‘very satisfied’ by the study, citing the ease of use and the increased autonomy and understanding of asthma as the main advantages. In total, 74% indicated that the system had helped to improve their ability to manage their symptoms. The most positive features of the telemedicine system were described as follows: increased awareness and information about asthma, improved ability to monitor/manage the condition with the feedback screens on the mobile phone and ease of use.
Meeting government objectives for telecare in moving from local implementation to mainstream services
Authors: Barlow James , Bayer Steffen , Castleton Beverly , Curry Richard
Published: July 2005

The UK government wishes to deploy a mainstream telecare service by 2010. We believe that it will be necessary to overcome the organizational and structural barriers to such an implementation. A better understanding of the effect of telecare across the care system as a whole will also be needed. In the absence of rigorous data from trials and because of the time taken for systemic effects to emerge, the evidence for the benefits of telecare needs to be explored through simulation modelling.
School nurse, family and provider connectivity in the FITE diabetes project
Authors: Malasanos Toree H , Patel Bhavin D , Klein Jay , Burlingame Julie B
Published: July 2005

The Florida Initiative in Telehealth and Education (FITE) diabetes project includes a system of remote blood glucose monitoring and online education for school personnel, families and providers. Forty-four patients with diabetes (100% of patients), six caregivers, six case managers and 18 school nurses were provided with secure email access, allowing blood glucose and other data transfer. In all, 50% of school nurses and 100% of case managers completed educational modules on the FITE Website. Over 90% of patients and all school nurses received equipment for transmitting blood glucose data to their computers. The data were discussed during clinic appointments. Inclusion of previously unavailable data from school nurses contributed to fine-tuning the diabetes management regimen. Those patients, families and school nurses who chose to transmit blood glucose data and participate in online education expressed satisfaction with the technology, the process and the improved communication.
Misconceptions surrounding videoconferencing
Authors: Padgham K , Scott J , Krichell A , Mceachen T , Hislop L
Published: July 2005

We carried out a study to assess the level of training required by hospital staff to operate a videoconferencing system. Fifty members of hospital staff, who had no previous videoconferencing experience, were studied. When using simple pictorial instructions, they took on average just under 6 min to connect successfully to a remote site. Male subjects connected faster (average 309 s) than female subjects (385 s; P<0.01). Subjects of 40 years or younger connected faster (average 311 s) than those over 40 years (average 398 s; P<0.02). Only three individuals (6%) required supplementary help via the telephone. Dedicated training may not be necessary when simple pictorial instructions are available to the operator.
Evaluation of the practical feasibility and acceptability of home monitoring in residential homes
Authors: Bratan Tanja , Clarke Malcolm , Jones Russell , Larkworthy Andrew , Paul Ray
Published: July 2005

Three residential homes to the north-west of London, with their associated medical centres, were equipped with telemonitors to measure several variables, including seven-lead electrocardiogram, blood pressure, oxygen saturation, heart rate, temperature and respiration. The monitors could be operated by non-medical personnel. After recording, the data were transmitted via the Internet to a server. A total of 24 patients with a variety of chronic conditions were monitored regularly for a period of one year. Data transmission was found to be unreliable on occasions and was improved by extending the wireless network in the homes. Data access and presentation were considered acceptable, although suggestions for minor changes were made. No discernible impact on disease management, diagnosis or care was observed as a result of the monitoring. However, interviewees saw several potential benefits and patient acceptance was very good. The monitoring was found to be generally acceptable and feasibility was considered to have been largely proven.