bluuebunny/crossref_metadata_2025_split huggingface dataset:
MGLuR5 activation reduces β‐amyloid‐induced cell death in primary neuronal cultures and attenuates translocation of cytochrome c and apoptosis‐inducing factor
Authors: Movsesyan Vilen A. , Stoica Bogdan A. , Faden Alan I. 
Published: June 2004

AbstractActivation of metabotropic glutamate receptor 5 (mGluR5) has been shown to reduce caspase‐dependent apoptosis in primary neuronal cultures induced by staurosporine and etoposide. β‐Amyloid (Aβ)‐induced neurotoxicity in culture appears to be in part caspase mediated. In the present studies the effects of treatment with an mGluR5 agonist or antagonist on Aβ‐induced neuronal apoptosis were examined in rat cortical neuronal cultures. Pretreatment with the selective mGluR5 agonist (RS)‐2‐chloro‐5‐hydroxyphenylglycine (CHPG) markedly reduced the number of apoptotic cells after exposure to Aβ (25–35), as well as associated LDH release. Blockade of mGluR5 by the selective antagonist, 2‐methyl‐6‐(phenylethynyl)pyridine (MPEP) attenuated these effects of CHPG. A similar neuroprotective effect of mGluR5 activation by CHPG was observed in cultures treated with full‐length Aβ peptide (1–42). CHPG attenuated Aβ (25–35)‐induced cytochrome c release and decreased levels of active caspase‐3 protein. CHPG also reduced translocation of apoptosis‐inducing factor (AIF) induced by Aβ (25–35). Thus, mGluR5 activation limits the release of mitochondrial proteins associated with induction of both caspase‐dependent and ‐independent apoptosis.
In vivo inhibition of Aβ production by memapsin 2 (β‐secretase) inhibitors
Authors: Chang Wan‐Pin , Koelsch Gerald , Wong Stephen , Downs Deborah , Da Huining , Weerasena Vajira , Gordon Brian , Devasamudram Thippeswamy , Bilcer Geoffrey , Ghosh Arun K. , Tang Jordan 
Published: June 2004

AbstractWe have previously reported structure‐based design of memapsin 2 (β‐secretase) inhibitors with high potency. Here we show that two such inhibitors covalently linked to a ‘carrier peptide’ penetrated the plasma membrane in cultured cells and inhibited the production of β‐amyloid (Aβ). Intraperitoneal injection of the conjugated inhibitors in transgenic Alzheimer's mice (Tg2576) resulted in a significant decrease of Aβ level in the plasma and brain. These observations verified that memapsin 2 is a therapeutic target for Aβ reduction and also establish that transgenic mice are suitable in vivo models for the study of memapsin 2 inhibition.
Focal dysfunction of the proteasome: a pathogenic factor in a mouse model of amyotrophic lateral sclerosis
Authors: Kabashi Edor , Agar Jeffrey N. , Taylor David M. , Minotti Sandra , Durham Heather D. 
Published: June 2004

AbstractMutations in the Cu/Zn‐superoxide dismutase (SOD‐1) gene are responsible for a familial form of amyotrophic lateral sclerosis (fALS). The present study demonstrated impaired proteasomal function in the lumbar spinal cord of transgenic mice expressing human SOD‐1 with the ALS‐causing mutation G93A (SOD‐1G93A) compared to non‐transgenic littermates (LM) and SOD‐1WT transgenic mice. Chymotrypsin‐like activity was decreased as early as 45 days of age. By 75 days, chymotrypsin‐, trypsin‐, and caspase‐like activities of the proteasome were impaired, at about 50% of control activity in lumbar spinal cord, but unchanged in thoracic spinal cord and liver. Both total and specific activities of the proteasome were reduced to a similar extent, indicating that a change in proteasome function, rather than a decrease in proteasome levels, had occurred. Similar decreases of total and specific activities of the proteasome were observed in NIH 3T3 cell lines expressing fALS mutants SOD‐1G93A and SOD‐1G41S, but not in SOD‐1WT controls. Although overall levels of proteasome were maintained in spinal cord of SOD‐1G93A transgenic mice, the level of 20S proteasome was substantially reduced in lumbar spinal motor neurons relative to the surrounding neuropil. It is concluded that impairment of the proteasome is an early event and contributes to ALS pathogenesis.
NMDA‐receptor regulation of muscarinic‐receptor stimulated inositol 1,4,5‐trisphosphate production and protein kinase C activation in single cerebellar granule neurons
Authors: Young Kenneth W. , Garro M. Asier , Challiss R. A. John , Nahorski Stefan R. 
Published: June 2004

AbstractInositol 1,4,5‐trisphosphate (InsP3) production in single cerebellar granule neurons (CGNs) grown in culture was measured using the PH domain of phospholipase C δ1 tagged with enhanced green fluorescent protein (eGFP‐PHPLCδ1). These measurements were correlated with changes in intracellular free Ca2+ determined by single cell imaging. In control CGNs, intracellular Ca2+ stores appeared replete. However, the refilling state of these stores appeared dependent on the fluorophore used to measure Ca2+‐release. Thus, methacholine (MCH), acting via muscarinic acetylcholine‐receptors (mAchRs), mobilised intracellular Ca2+ in cells loaded with fluo‐3 and fura‐4f, but not fura‐2. Confocal measurements of single CGNs expressing eGFP‐PHPLCδ1 demonstrated that MCH stimulated a robust peak increase in InsP3, which was followed by a sustained plateau phase of InsP3 production. In contrast, glutamate‐induced InsP3 signals were weak or not detectable. MCH‐stimulated InsP3 production was reduced by chelation of intracellular Ca2+ with BAPTA, and emptying of intracellular stores with thapsigargin, indicated a positive feedback effect of Ca2+ mobilisation onto PLC activity. In CGNs, NMDA‐ and KCl‐mediated Ca2+‐entry significantly enhanced MCH‐induced InsP3 production. Furthermore, mAchR‐mediated PLC activation appeared sensitive to the full dynamic range of intracellular Ca2+ increases stimulated by 100 μm NMDA. This dynamic regulation was also observed at the level of PKC activation indicated by an enhanced translocation of eGFP‐tagged myristoylated alanine‐rich C kinase substrate (MARCKS) protein in cells stimulated with MCH. Thus, NMDA‐mediated Ca2+ influx and PLC activation may represent a coincident‐detection system whereby ionotropic and metabotropic signals combine to stimulate InsP3 production and PKC‐mediated phosphorylation events in CGNs.
Netrin‐1 is crucial for the establishment of the dorsal column‐medial lemniscal system
Authors: Kubota Chikara , Nagano Takashi , Baba Hisatoshi , Sato Makoto 
Published: June 2004

AbstractThe dorsal column‐medial lemniscal system is a significant sensory pathway that mediates touch and limb position sense. In this system, axons from the second‐order neurons in the dorsal column nuclei form the internal arcuate fibers, cross the ventral midline (floor plate) within the medulla oblongata, and then project to the thalamus as the medial lemniscus. Here we demonstrate that Netrin‐1, which is secreted from the floor plate in the medulla oblongata, is indispensable to the formation of the dorsal column‐medial lemniscal system. Axons from the dorsal column nuclei cross the midline at around embryonic day 11 in mice. Concurrently, Netrin‐1 mRNA and its receptor DCC (deleted in colorectal cancer) were expressed in the floor plate and commissural axons there, respectively. In our explant culture experiments, the floor plates of the embryonic 11‐day‐old mutant Netrin‐1 homozygous mice did not attract axons from the dorsal column nuclei of ICR mice, while those from the wild type littermates did. Moreover, we observed that although the dorsal column nuclei developed in situ in mutant mice, their axons were not attracted toward the floor plate: they did not cross midline and remained ipsilaterally, without forming the internal arcuate fibers, in embryonic 17‐day‐old mutant Netrin‐1 homozygous mice.
Endocannabinoids accumulate in spinal cord of SOD1G93A transgenic mice
Authors: Witting Anke , Weydt Patrick , Hong Soyon , Kliot Michel , Mőller Thomas , Stella Nephi 
Published: June 2004

AbstractApproximately 2% of amyotrophic lateral sclerosis (ALS) cases are caused by mutations in the super oxide dismutase 1 (SOD1) gene and transgenic mice for these mutations recapitulate many features of this devastating neurodegenerative disease. Here we show that the amount of anandamide (AEA) and 2‐arachidonoylglycerol (2‐AG), two endocannabinoids that have neuroprotective properties, increase in spinal cord of SOD1G93A transgenic mice. This increase occurs in the lumbar section of spinal cords, the first section to undergo neurodegeneration, and is significant before overt motor impairment. Our results show that chronic neurodegeneration induced by a genetic mutation increases endocannabinoid production possibly as part of an endogenous defense mechanism.
Different efficacy of mycophenolate mofetil as salvage treatment for acute and chronic GVHD after allogeneic stem cell transplant
Authors: Kim Jong Gwang , Sohn Sang Kyun , Kim Dong Hwan , Lee Nan Young , Suh Jang Soo , Lee Kun Soo , Lee Kyu Bo 
Published: June 2004

Abstract: Objective: The therapeutic options currently available for treating refractory graft‐vs.‐host disease (GVHD) are limited. Therefore, the present study evaluated the efficacy of mycophenolate mofetil (MMF) as a salvage treatment for acute and chronic GVHD in allograft patients.Methods: Twenty‐six consecutive patients with refractory acute (13 patients) or chronic (13 patients) GVHD were enrolled. The first‐line treatment for all patients with acute GVHD consisted of a combination of cyclosporine A (CyA) and steroids, while the first‐line treatment for chronic GVHD was steroids with or without CyA according to the risk group. MMF was added at a dose of 1.5 or 2 g daily and the steroids were tapered in the refractory cases.Results: Four (30.8%) of 13 patients with refractory acute GVHD responded to MMF. When analyzing the overall results according to the type of acute GVHD, improvement was observed in four (30.8%) of 13 skin cases, four (44.4%) of nine liver cases, and two (22.9%) of nine gut cases. Ten (76.9%) of 13 patients with refractory chronic GVHD responded to MMF. The common side effects were gastrointestinal disturbance (26.9%) or infectious complications (23.1%). The estimated 2‐yr survival rate for patients with acute GVHD and chronic GVHD was 33.3% and 53.9%, respectively.Conclusions: MMF would appear to be effective and safe for treating refractory chronic GVHD, yet not as effective for treating refractory acute gut GVHD. Accordingly, a prospective randomized clinical trial is warranted to assess the impact of MMF in the treatment of refractory GVHD.
Disease‐ or therapy‐related bone marrow damage cannot be overcome by changes in stem cell source or dose in allogeneic transplantation
Authors: Novotny J. R. , Rosenthal C. , Elmaagacli A. H. , Dürig J. , Beelen D. W. , Dührsen U. 
Published: June 2004

Abstract:  Objective:  To test whether the functional impairment of the host bone marrow (BM) microenvironment pre‐existing at the time of transplantation could be overcome by the increased content of immature cells in allogeneic peripheral blood stem cell transplantation (PBSCT) when compared with bone marrow transplantation (BMT).Methods:  Cobble stone area forming cells (CAFC) were assayed in normal BM and BM after allogeneic BMT and PBSCT after stable engraftment. Groups were compared by two‐tailed t‐test.Results:  While BM from 11 normal controls contained an average of 778.8 CAFC‐d35 per 106 low density bone marrow cells (LDBMC, range 453–1231 per 106 LDBMC), BM from patients after BMT contained an average of 123.7 CAFC‐d35 per 106 LDBMC (range 38–257) per 106 LDBMC. BM from patients transplanted with PBSC after myeloablative conditioning contained 128.3 (range 46–305) CAFC‐d35 per 106 LDBMC (P = 0.89 compared with BMT). Similar results were obtained when patients after PBSCT with non‐myeloablative conditioning were included (P = 0.62 compared with BMT). CAFC numbers in patients transplanted in early stages of myeloid leukaemia (acute myeloid leukaemia first remission, chronic myeloid leukaemia first chronic phase) were significantly higher than CAFC numbers in patients transplanted in more advanced stages (P = 0.008) or myelodysplastic syndrome (P = 0.023). The lowest CAFC numbers were found in two cases of retransplantation.Conclusion:  Our findings indicate that the functional state of the BM microenvironment rather than stem cell dose or source is limiting for the homing and engraftment of immature haemopoietic cells in clinical transplantation.
The application of North American CT scan criteria to an Australian population with minor head injury
Authors: Rosengren David , Rothwell Sean , Brown Anthony FT , Chu Kevin 
Published: June 2004

AbstractObjective:  To determine potential changes in the number of CT head scans performed if the New Orleans Criteria (NOC) or Canadian CT Head Rule (CCTR) was applied to an Australian emergency department population of minor head injured (MHI) patients.Methods:  A retrospective chart review was conducted in an adult metropolitan teaching hospital in Brisbane. All patients presenting over a 3‐month period with a GCS Score of 15 following an MHI and had a CT head scan performed were selected for analysis. Using clinically significant CT abnormalities and neurological intervention as the outcome measures, the NOC and CCTR were applied to determine if CT scanning was considered necessary.Results:  Of the 240 patients reviewed, 230 had a normal CT scan and 10 had clinically significant CT abnormalities. One patient with CT abnormality required neurosurgical intervention. Application of the NOC would have resulted in a 3.8% (95% CI 1.7–7.0%) reduction in CT scans performed without missing any patients with CT abnormalities or requiring neurological intervention. Application of the CCTR using both high and low risk factors would have resulted in a 46.7% (95% CI 40.2–53.2%) reduction in CT scans performed without missing the patient requiring neurological intervention, but would not have detected two patients with clinically significant CT abnormalities.Conclusion:  Neither the NOC nor the CCRT appear suitable for significantly reducing the number of normal CT head scans performed without missing clinically significant CT abnormalities when applied to our current clinical practice.
Wheeze and mediastinal mass: A challenging patient
Authors: Heinz Peter , Dunne John 
Published: June 2004

AbstractAirway obstruction is a recognized complication in children with mediastinal masses. They typically present with difficulty in breathing and associated respiratory noises. General anaesthesia in these patients can lead to complete airway obstruction with fatal consequences. Successful management in the ED necessitates rapid recognition of the underlying problem and appropriate intervention. We report the case of a 7‐year‐old boy presenting with respiratory collapse and describe the management that led to successful resuscitation.
Not just gastroenteritis: Thyroid storm unmasked
Authors: Charles Rabind Antony , Goh Su‐Yen 
Published: June 2004

AbstractEstablishing the diagnosis of thyroid storm is difficult in the ED, especially where there is no antecedent history of thyroid disease or clinical clues like goitre, exophthalmos or altered mentation, yet early recognition and treatment are essential in reducing mortality and morbidity from this endocrine emergency. We present a case where suspected infective gastroenteritis in a newly diagnosed diabetic masked the major symptomatology of thyroid storm, and review the diagnosis and management of thyrotoxic crisis.
A casemix model for estimating the impact of hospital access block on the emergency department
Authors: Stuart Peter 
Published: June 2004

AbstractObjective: To determine the ED activity and costs resulting from access block.Methods: A casemix model (AWOOS) was developed to measure activity due to access block. Using data from four hospitals between 1998 and 2002, ED activity was measured using the urgency and disposition group (UDG) casemix model and the AWOOS model with the purpose of determining the change in ED activity due to access block.Results: Whilst the mean length of stay in ED (admitted patients) increased by 93% between 1998 and 2002, mean UDG activity increased by 0.63% compared to a mean increase in AWOOS activity of 24.5%. The 23.9% difference between UDG and AWOOS activity represents the (unmeasured) increase in ED activity and costs for the period 1998–2002 resulting from access block.Conclusion: The UDG system significantly underestimates the activity in EDs experiencing marked access block.
Intermediate dose metoclopramide is not more effective than standard dose metoclopramide for patients who present to the emergency department with nausea and vomiting: A pilot study
Authors: Cham Swee , Basire Mary , Kelly Anne‐Maree 
Published: June 2004

AbstractObjective:  To determine whether intermediate dose metoclopramide is more effective than standard dose metoclopramide for patients who present to the ED with nausea and vomiting.Methods:  This prospective, single‐blind, randomized trial was conducted in the ED of two community teaching hospitals in a convenience sample of adult patients who presented to ED with nausea and vomiting. Patients were randomized to receive either 10 mg metoclopramide IV or 0.4 mg/kg IV (up to a maximum dose of 32 mg). The outcomes measured were: change in nausea score (measured on a 11‐point verbal rating scale), requirement for other anti‐emetic drug administration, and presence of side‐effects.Results:  Fifty‐eight patients were eligible for analysis (34 in 10 mg group and 24 in 0.4 mg/kg group). Median reduction in nausea score in 10 mg group was four (range 0–10, 95% CI 3–5) compared with five for 0.4 mg/kg group (range −1–10, 95% CI 4–6). This difference was not statistically significant (P = 0.629). Five patients in the 10 mg group required rescue anti‐emetic, compared with three in the 0.4 mg/kg group (P = 1.00). There were no side‐effects in the 10 mg group and two in the 0.4 mg/kg group.Conclusion:  This study suggests that there is no difference in effectiveness between 10 mg and 0.4 mg/kg of metoclopramide in the ED population with nausea and vomiting.
Elevation of cardiac troponins in exacerbation of chronic obstructive pulmonary disease
Authors: Harvey Martyn G , Hancox Robert J 
Published: June 2004

AbstractObjectives:   To investigate the prevalence of serum troponin elevation in patients admitted to hospital with an exacerbation of chronic obstructive pulmonary disease (COPD).Methods:  We examined the records of all patients admitted to hospital for treatment of COPD for serum troponin measurement, clinical features of myocardial ischaemia, oxygenation (pulse oximetry, arterial blood gas analysis), spirometry, and duration of admission.Results:  Troponin elevation was observed in 58 of 235 (25%) presentations in which troponin was measured. Despite the troponin result, only seven of these 58 patients had been diagnosed with an acute coronary syndrome. New ECG evidence of ischaemia was uncommon. Patients with raised troponins tended to be older (75.7 vs 70.0 years, P = 0.001), had lower pulse oximetry (85.6% vs 89.6%, P = 0.003), were more acidotic (pH 7.34 vs 7.40, P= 0.002) and more hypercapnoeic (pCO2 58.0 vs 49.1, P = 0.04). There were no significant differences in serum creatine kinase. Patients with raised troponins had significantly longer admissions (5 vs 3 days, P = 0.001).Conclusions:  Serum troponins are commonly raised in acute exacerbations of COPD and appear to reflect the severity of the exacerbation. In the majority of patients there is insufficient evidence to support the diagnosis of an acute coronary syndrome.
Risk factors for recent domestic physical assault in patients presenting to the emergency department
Authors: Stuart Peter 
Published: June 2004

AbstractObjective:  To identify risk factors for physical or sexual assault as a result of domestic violence in patients presenting to the ED.Methods:  Backward prevalence study of two urban teaching hospital emergency departments measuring the 1‐year period prevalence, acute incidence of ED presentation and risk factors of domestic physical assault.Results:  Of the 1326 patients (62% female) completing the study, 115 (9% CI 7%, 10%) reported assault by a partner or ex‐partner within the preceding 12 months and 31 (2% CI 1.6%, 2.3%) reported domestic physical assault as the cause of their presentation. Risk factors for recent domestic physical assault included female gender (prevalence rate ratio, (PRR) 1.5 CI 1.0 2.2), age 17 to < 25 years (PRR 6.8 CI 1.7 27.7) or 25 to < 35 years (PRR 5.7 CI 1.4 23.0), past presentation to an ED for assault (PRR 2.5 CI 1.7 3.7) and a past history of child abuse (PRR 2.2 CI 1.5 3.1). There was no association between health service utilization or mental illness and the reporting of recent domestic physical assault.Conclusion:  The study characterizes ED patients at high risk of injury from domestic violence.
Infantile Henoch‐Schönlein purpura
Authors: Wong Christina T , Harrington John W 
Published: June 2004

AbstractWe present an infant with generalized palpable purpura, arthritis and fever, whose findings were atypical for classic childhood Henoch‐Schönlein purpura (HSP). By describing the clinical symptoms and prognostic differences seen in infants versus school age children, we encourage physicians to be aware of infantile HSP in their differential diagnosis when they encounter a non‐toxic infant with generalized purpura.
The changing role of the emergency department in the Northern Territory: A Delphi study
Authors: Meuleners Lynn B , Lee Andy H , Zhao Yuejen , Intrapanya Methinee 
Published: June 2004

AbstractObjective:  To explore the changing role of EDs in Northern Territory hospitals.Methods:  A two‐round Delphi study was undertaken by recruiting a panel of health professionals from the EDs of the five Northern Territory public hospitals. Participants in round one were asked to list changes they have encountered and how these changes have affected health service delivery, as well as five factors that were responsible for the changes. During the second round they prioritized the factors identified in order of importance.Results:  Twenty‐four ED staff returned their questionnaire. Global changes identified were more verbal/physical abuse from patients, followed by increase in acuity of patient presentations. The most important factor perceived as responsible for the changes was budget cuts, resulting in fewer inpatient beds, an increase in access block and sicker patients being discharged too early.Conclusion:  The Delphi evaluation provided insights into the problems facing the ED from the staff perspective and offered some suggestions to deal with the emerging issues.
Glyphosate herbicide formulation: A potentially lethal ingestion
Authors: Stella Julian , Ryan Matthew 
Published: June 2004

AbstractGlyphosate surfactant herbicide (GlySH) toxicity is an uncommon poisoning. We report two fatalities involving suicidal ingestion of this herbicide. Both deaths occurred despite early recognition of the serious nature of the poisoning and aggressive treatment. The deaths in this series are analysed in the context of a review of existing literature. Although traditionally regarded as minimally toxic, many deaths have been reported following suicidal ingestion. Severe GlySH toxicity may be refractory even to the most intensive supportive care. The triad of pulmonary oedema, metabolic acidosis and hyperkalaemia portends poor outcome. While containing a carbon phosphorus moiety, GlySH does not exhibit organophosphate toxicity. A clinical guide to assessing severity of GlySH toxicity is proposed and treatment modalities discussed.