bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes occurring in cortical NO release and brain NO‐synthases during a paradoxical sleep deprivation and subsequent recovery in the rat
Authors: Clément Pierre , Sarda Nicole , Cespuglio Raymond , Gharib Abdallah 
Published: July 2004

AbstractVariations occurring in cortical nitric oxide (NO) release were analysed with a voltametric method in rats (i) placed in control conditions, (ii) while being paradoxical sleep deprived (PSD), or (iii) recovering from a PSD. Activities of neuronal (nNOS) and inducible (iNOS) NO‐synthases as well as nNOS expression were also determined in several brain regions. In baseline conditions, circadian variations in nNOS expression and activity were maximal during the dark period and minimal during the light one for all the structures analysed (frontal cortex, pons and medulla). In the same way, cortical NO release occurred through a circadian rhythm exhibiting maxima and minima during dark and light periods, respectively. In the same experimental conditions, iNOS activity did not exhibit time‐dependent changes. The correlative changes observed in baseline conditions between NO release, nNOS expression and activity within the frontal cortex were disrupted during PSD and subsequent recovery. Still again, iNOS activity remained unchanged. Results obtained point out that the tight coupling existing in control conditions between nNOS expression‐activity and NO release is disrupted by a PSD and remains affected during the subsequent 24 h recovery. Their significance is discussed.
Organic anion transporter 3 is involved in the brain‐to‐blood efflux transport of thiopurine nucleobase analogs
Authors: Mori Shinobu , Ohtsuki Sumio , Takanaga Hitomi , Kikkawa Tazuru , Kang Young‐Sook , Terasaki Tetsuya 
Published: July 2004

AbstractThiopurines are used as antileukemic drugs. However, during chemotherapy CNS relapses occur due to the proliferation of leukemic cells in the CNS resulting from restricted drug distribution in the brain. The molecular mechanism for this limited cerebral distribution remains unclear. The purpose of this study was to identify the transporter responsible for the brain‐to‐blood transport of thiopurines across the blood–brain barrier (BBB) using the brain efflux index method. [14C]6‐Mercaptopurine (6‐MP) and [3H]6‐thioguanine were eliminated from rat brain in a time‐dependent manner. The elimination of [14C]6‐MP was inhibited by substrates of rat organic anion transporters (rOATs), including indomethacin and benzylpenicillin. rOAT1 and rOAT3 exhibited 6‐MP uptake, while benzylpenicillin inhibited rOAT3‐mediated uptake, but not that by rOAT1. rOAT3‐mediated [14C]6‐MP uptake was also inhibited by other thiopurine derivatives. Although methotrexate inhibited rOAT3‐mediated [14C]6‐MP uptake, the Ki value was 17.5‐fold greater than the estimated brain concentration of methotrexate in patients receiving chemotherapy. Accordingly, 6‐MP would undergo efflux transport by OAT3 from the brain without any inhibitory effect from coadministered methotrexate in the chemotherapy. In conclusion, rOAT3 is involved in the brain‐to‐blood transport of thiopurines at the BBB and is one mechanism of limited cerebral distribution.
Phosphorylated p38MAPK specific antibodies cross‐react with sarkosyl‐insoluble hyperphosphorylated tau proteins
Authors: Sahara Naruhiko , Vega Irving E. , Ishizawa Takashi , Lewis Jada , McGowan Eileen , Hutton Michael , Dickson Dennis , Yen Shu‐Hui 
Published: July 2004

AbstractNeurofibrillary tangles (NFT) accumulated in Alzheimer's diseases and related disorders contain hyperphosphorylated tau and display immunoreactivity for active forms of various kinases. To understand the role of p38MAPK (mitogen‐activated protein kinase) in NFT formation, we have studied a transgenic (Tg) mouse model of tauopathy, JNPL3, that expresses P301L mutant tau, and bigenic mice, TAPP, generated by cross‐breeding of JNPL3 with Tg2576 mice. Age‐matched non‐Tg mice (NTg), wild‐type human tau Tg mice (JN25), and Tg2576 mice were used as controls. Phosphorylated p38MAPK (active form) immunoreactivity was consistently located in NFT and granulovaculolar degeneration in JNPL3 and TAPP mice older than 5 months of age. Unphosphorylated/total‐p38MAPK was not detectable in spinal cord and brain sections from 2‐ to 11‐month‐old mice, even though JNPL3 mice, but not controls had an age‐dependent increase of total‐p38MAPK by western blotting. Spinal cord/brain extracts from mice and human with tauopathy were demonstrated to have insignificant amount of active‐p38MAPK. However, they contained antiactive‐p38MAPK cross‐reactive proteins insoluble in sarkosyl and similar to phosphorylated tau in size. Consistently, antiactive‐p38MAPK immunoprecipitates displayed tau immunoreactivity, but not total‐p38MAPK, and antitau immunoprecipitates displayed active‐p38MAPK immunoreactivity. Together, the results indicate that the cross‐reactivity of antiactive‐p38MAPK antibody with phosphorylated tau is responsible for the immunolabeling of tau‐positive inclusion.
Regulation of dopamine D1‐receptor activation in vivo by protein phosphatase 2B (calcineurin)
Authors: Adlersberg Mella , Hsiung Shu‐chi , Glickstein Sara B. , Liu Kuo‐peing , Tamir Hadassah , Schmauss Claudia 
Published: July 2004

AbstractMice lacking dopamine D2 receptors exhibit a significantly decreased agonist‐promoted forebrain neocortical D1 receptor activation that occurs without changes in D1 receptor expression levels. This raises the possibility that, in brains of D2 mutants, a substantial portion of D1 receptors are uncoupled from their G protein, a phenomenon known as receptor desensitization. To test this, we examined D1‐agonist‐stimulated [35S]GTPγS binding (in the presence and absence of protein phosphatase inhibitors) and cAMP production (in the presence and absence of pertussis toxin) in forebrain neocortical tissues of wild‐type mice and D2‐receptor mutants. These studies revealed a decreased agonist‐stimulated G‐protein activation in D2 mutants. Moreover, whereas protein phosphatase 1/2A (PP1/2A) and 2B (PP2B) inhibitors decrease [35S]GTPγS binding in a concentration‐dependent manner in wild type, they have either no (PP2B) or only partial (PP1/2A) effects in D2 mutants. Furthermore, for D2 mutants, immunoprecipitation experiments revealed increased basal andD1‐agonist‐stimulated phosphorylation of D1‐receptor proteins at serine residues. Finally, D1 immunoprecipitates of both wild type and D2 mutants also contain protein kinase A (PKA) and PP2B immunoreactivities. In D2 mutants, however, the catalytic activity of the immunoprecipitated PP2B is abolished. These data indicate that neocortical D1 receptors are physically linked to PKA and PP2B and that the increased phosphorylation of D1 receptors in brains of D2 mutants is due to defective dephosphorylation of the receptor rather than increasedkinase‐mediated phosphorylation.
Learning and performing care management: experiences of a newly formed interdisciplinary, assessment and rehabilitation team
Authors: Kneafsey Rosie , Long Andrew , Reid Gaynor , Hulme Claire 
Published: July 2004

AbstractDevelopments in primary and intermediate care services have enhanced interest in the notion of care management, the processes that it encompasses and the challenges that it poses to practitioners who are more used to working in a uni‐ or multidisciplinary manner. This article explores the way that a set of practitioners, new to care management, coped with the challenges of working within a newly created care‐managed assessment and rehabilitation service for older people in one UK county. Data were gathered via non‐participant observation, and group and individual interviews, as part of a wider action‐research evaluation study. Three themes emerged from the data: the processes of ‘learning’ to become a care manager; ‘doing’ care management; and ‘experiences’ of the role. In order to ‘learn’ care management, staff needed to develop a range of new skills, establish supportive care‐management processes, develop a new identity and work in an interdisciplinary way. ‘Doing’ care management involved working with a small group of patients with complex needs and precarious levels of homeostasis. Problem solving and crisis management were key activities and often required a creative approach to practice. Although care managers derived great satisfaction from their role, their ‘experiences’ were characterized by stress and anxiety. The practitioners from healthcare backgrounds needed more preparation to adapt to their new levels of responsibility and client risk. Successful management of the transition to care manager requires support from the key stakeholders and strong leadership within care manager teams. In‐house competency‐based training and induction programmes, and mentorship, can also play an important role, together with innovative forms of postqualifying education and training, for example, via job exchanges or an apprenticeship model.
Hepatocyte growth factor and c‐Met expression in rat and human liver fibrosis
Authors: Cramer Thorsten , Schuppan Detlef , Bauer Michael , Pfander David , Neuhaus Peter , Herbst Hermann 
Published: July 2004

Abstract:  Background: Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes in vitro.Aims: Substitution of HGF was suggested for human liver disease on the basis of animal experiments. The cellular sources of HGF and its receptor, c‐Met, in liver disease in vivo are not well defined.Methods: We characterised HGF and c‐Met expression in normal and cirrhotic human livers and rat livers at various time points after CCl4 administration by in situ hybridisation and immunohistology. HGF transcripts were restricted to resting and activated stellate cells in rat and human liver.Results: In rat liver, HGF showed peak levels 6–12 h following acute intoxication, and remained increased after repeated CCl4 injury. HGF transcript levels were very low in normal human liver, but excessively raised in fibrosis/cirrhosis. In contrast, HGF immunoreactivity was found not only in perisinusoidal/periductular cells but also in cholangiocytes of proliferating ductules. c‐Met RNA and protein was expressed in hepatocytes, cholangiocytes, and arteriolar endothelial cells.Conclusions: The HGF‐specific immunostaining of proliferating cholangioles in the absence of HGF RNA suggests c‐Met‐mediated uptake of HGF and paracrine stimulation of cholangiocellular proliferation. Mitogenic effects of HGF on hepatocytes may therefore be accompanied by undesired cholangiogenesis and angiogenesis limiting its therapeutic value in chronic liver disease.
Serum levels of soluble molecules associated with evasion of immune surveillance: a study in biliary disease
Authors: Enjoji Munechika , Yamaguchi Koji , Nakashima Manabu , Ohta Satoshi , Kotoh Kazuhiro , Fukushima Marie , Kuniyoshi Masami , Tanaka Masao , Nakamuta Makoto , Watanabe Takeshi , Nawata Hajime 
Published: July 2004

Abstract:  Background: Biliary carcinoma cells produce the transmembrane proteins, Fas, FasL, and RCAS1. It has been demonstrated that the Fas/FasL and RCAS1 systems induce apoptosis of activated immune cells and that the soluble isoforms of these proteins (sFas, sFasL, and sRCAS1) also exhibit this function.Methods: We measured serum levels of these soluble‐types in patients with biliary disease by ELISA and investigated their clinical significance.Results: In some cases of cholangitis and autoimmune biliary disease, serum sFasL values were over 0.1 ng/ml but the protein was undetectable in any patients with biliary carcinoma. sFas levels were significantly higher in the autoimmune disease (mean, 6.83 ng/ml) and cancer (mean, 6.42 ng/ml) groups than in the cholangitis group (mean, 4.23 ng/ml) and normal controls (mean, 2.93 ng/ml). However, the sFas values in malignancy did not correlate with the progression of clinical stage. The percentage positive for serum sRCAS1 was 9.7% in benign disease but was 63.4% in cancer.Conclusions: Our data suggest that serum sFasL in biliary disease may be derived predominantly from activated immune cells and not from cancer cells and that autoimmune biliary disease may be mediated by the Fas/FasL apoptotic system. sRCAS1 is highly tumor‐specific and may be of value in the diagnosis of malignancy.
Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse
Authors: LUDLOW Joanne P. , EVANS Sharon F. , HULSE Gary 
Published: July 2004

AbstractObjective:  To determine the obstetric and perinatal outcomes of women using illicit drugs during pregnancy by substance group.Method:  A retrospective audit of obstetric and perinatal outcomes in women who used opiates or amphetamines during their pregnancy and delivered at King Edward Memorial Hospital (KEMH), Perth, Australia between December 1997 and April 2000 was performed. Maternal, fetal and neonatal parameters were assessed. These were compared with obstetric and perinatal data recorded by the Health Department of Western Australia (HDWA) for the 25 291 deliveries of 25 677 infants in 1998.Results:  Between December 1997 and April 2000 91 opiate‐using and 50 amphetamine‐using women were identified and included in the analysis. Both groups of drug‐using women were younger (opiates P = 0.001, amphetamines P = 0.001) than the general population. There was a higher incidence of aboriginality (P = 0.001) in the amphetamine group. In the opiate‐using group multiparity (P = 0.0001) and anaemia (P = 0.0001) were higher. Illicit drug‐using women had a higher incidence of hepatitis C (opiates P = 0.001, amphetamines P = 0.003), and a greater need for pharmacological analgesia for labour and delivery (opiates P = 0.007, amphetamines P = 0.042). Their infants were significantly more likely to deliver at less than 37 weeks’ gestation (opiates P = 0.0001, amphetamines P = 0.001), to have a birthweight of less than 2.5 kg (P = 0.0001), be small for gestational age and require admission to the special care nursery (P = 0.0001). Infants born to women in the amphetamine group were more likely to have an Apgar score <7 (P = 0.0001) recorded. Infants of women in the opiate group required more resuscitation (P = 0.05).Conclusion:  Women who use illicit drugs are more likely to experience adverse obstetric and perinatal outcomes than women in the general population. Differences are seen depending on the type of illicit drug used. These findings need to be replicated in a larger prospective cohort to highlight management requirements of these women and their infants. Further information is required about the effects of amphetamines in pregnancy.
Women's antenatal knowledge and plans regarding intrapartum pain management at the Royal Hospital for Women
Authors: HENRY Amanda , NAND Swaran L. 
Published: July 2004

AbstractAims:  To examine women's knowledge and antenatal plans regarding intrapartum pain management options at Royal Hospital for Women (RHW), Sydney, Australia.Methods:  From October 2002 to January 2003 women aged over 16 who had been in labour were given a questionnaire to complete in the first week post‐partum regarding intrapartum pain management. This included questions regarding their antenatal knowledge and predetermined plans.Results:  There were 496 participating women (69% response rate). Antenatal pain management information was accessed by 98% of women. Sources most accessed were antenatal classes (55%), multimedia (53%), and friends/relatives (46%). Sixty percent of women felt ‘very well informed’ antenatally. Women felt better informed antenatally if married/defacto, university educated, privately insured, or receiving birth centre care. Antenatally, 80% planned to use intrapartum pain management: ‘natural’ methods were most popular (62% planned to use), and pethidine least (49% planned against). The most common determinant against using medical methods was possible maternal side‐effects. Intrapartum, 19% used ‘unwanted’ pain management, mostly (67%) due to increased labour pain. Increased information access was associated with significantly higher use of both ‘natural’ methods and epidural analgesia, as well as significantly higher satisfaction scores.Conclusions:  Almost all women at RHW access information antenatally about intrapartum pain management, often from informal sources. Demographic factors affected type of information accessed and women's plans. Adequate access to information affected use of, and satisfaction with, pain management.
Tissue trauma after vaginal hysterectomy and colporrhaphy versus abdominal hysterectomy: A randomised controlled study
Authors: AKA Nurettin , KÖSE Gültekin , GÖNENÇ Isik , API Murat 
Published: July 2004

AbstractObjective:  As the magnitude of tissue trauma can be detected by measuring the blood levels of acute phase reactants, we aimed to evaluate tissue trauma markers after abdominal hysterectomy (AH) and vaginal hysterectomy (VH). We hypothesised that VH will be associated with a reduced increase in the level of acute phase reactants than AH.Methods:  Thirty women out of 92 patients scheduled for hysterectomies between June 2002 and June 2003 were randomised into two equal groups (n = 15) of VH and AH. Their levels of C‐reactive protein (CRP), α1‐antitrypsin (α1‐AT) and myoglobin (M) were analysed preoperatively and on the second, fourth and sixth days.Results:  In both methods of hysterectomy, the operating time (85.3 ± 6.57 min in the VH group vs 69 ± 7.54 min in the AH group, P < 0.0001), and hospital stay duration (7.2 ± 2.5 days in the AH group, 3.1 ± 1.1 days in the VH group, P < 0.0001) were highly significantly different from each other. Demographic parameters and other parameters which may affect tissue trauma markers were not statistically significantly different in each group. Postoperative increases in all markers were markedly high and showed a high statistical difference in both groups (P < 0.05). The postoperative CRP and M values in both groups were significantly higher in the AH group on the second and fourth days and on the sixth day for M only, whereas α1‐AT levels were only statistically different on the second day. The tissue trauma markers returned to normal levels on the sixth postoperative day for M, although there still was a statistically significant difference, but remained higher than normal for α1‐AT and CRP.Conclusion:  Whenever possible, VH should replace AH because this technique leads to a shorter hospital stay and less tissue trauma, enabling patients to return to their normal lives.
Ehlers–Danlos Syndrome (EDS) focusing on oral symptoms: a questionnaire study
Authors: Hagberg C , Berglund B , Korpe L , Andersson‐Norinder J 
Published: July 2004

Structured AbstractAuthors – Hagberg C, Berglund B, Korpe L, Andersson‐Norinder JObjectives – To study the prevalence of oral problems reported among a large group of adults with Ehlers–Danlos Syndrome (EDS). Furthermore, to compare proportions of disorders and general psychological well‐being with those in a cohort of randomized population‐based controls.Design – A questionnaire study.Setting and Sample Population – A total of 265 persons with EDS (response rate 77%) and 750 controls (response rate 63%) in a population‐based cohort. Sixty persons were excluded from the EDS group (support members, children, undiagnosed EDS) leaving a final study group of 144 adults. The final control group consisted of 331 persons since many had sent back unanswered questionnaires.Experimental Variables – Questions concerning general and oral symptoms, VAS scales for masticatory muscle pain ratings and General Health Questionnaire (GHQ12) questions were included.Outcome Measure – Proportions of affirmative answers in EDS group and controls were compared. Mean values for ratings on VAS scales. Proportions of GHQ12 scores with a threshold score of four or more.Results – The proportions of affirmative answers for persons with EDS concerning general health problems, oral problems and masticatory muscle symptoms were significantly higher compared with controls. In the EDS group those who had daily pain in the masticatory muscles had significantly higher mean values on the VAS scales compared with those who had pain a few days per month. A GHQ12 score of four or more was significantly more common in the EDS group than in the controls, suggesting that a decline in psychological well‐being was also more common in this group.Conclusion – It is important that dental practitioners should be aware of the oral problems associated with EDS and the impact the disease has on quality of life.
Audit as a learning tool in postgraduate emergency medicine training
Authors: Brazil Victoria 
Published: July 2004

AbstractObjective:  Educational activities for emergency medicine trainees need to be clinically focused, relevant, and ideally have the capacity to change practice and patient outcomes. It is proposed that the use of audit methods in educational sessions may address these learning needs. The aims of this project were to involve emergency medicine trainees in undertaking audits of ED patient care, and to evaluate the use of this technique in fulfilling training needs.Methods:  Trainees were given clinical topics on which to develop a presentation at weekly education sessions within the ED. This presentation included a brief clinical audit concerning an aspect of the same topic. The audit question addressed one of the issues identified as standard of care in the trainee presentation and investigated our department's level of compliance with that standard. At the end of a 6‐month period, a questionnaire was given to all trainees involved, either as presenters or attendees at an audit presentation.Results:  Trainees performing audits reported that this method was most useful for demonstrating the limitations of coding, giving a greater appreciation of poor documentation in medical records, and improving their presentation skills. Most trainees attending audit based presentations reported that this educational method gave them a greater appreciation of systems based practice, actually changed their clinical practice, and was more useful than traditional lectures.Conclusions:  Audit should be a key component of emergency medicine education. Trainees perceive the technique as useful addressing a number of training needs in a clinical context.
Responding to formal complaints about the emergency department: Lessons from the service marketing literature
Authors: Doig Gavan 
Published: July 2004

AbstractThe ability to respond to formal complaints is a necessary part of emergency medicine practice. In spite of the significance of formal complaints there is little guidance within the medical literature to understand why patients complain or how to provide satisfaction to individuals who complain. Practitioners are usually left to their own devices in the style and substance of complaint responses even when working within a defined complaint management system. This article draws on relatively abundant literature in the service marketing field to provide an understanding of dissatisfaction, complaining and complaint handling. Having developed an appropriate theoretical framework the article provides guidance for applying these concepts in dealing with formal complaints.