bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tramadol for prevention of postanaesthetic shivering: a randomised double‐blind comparison with pethidine
Authors: Mohta M. , Kumari N. , Tyagi A. , Sethi A. K. , Agarwal D. , Singh M. 
Published: December 2008

SummaryThe present study was conducted with the aims of comparing intravenous tramadol 1, 2 and 3 mg.kg−1 with pethidine 0.5 mg.kg−1 for prophylaxis of postanaesthetic shivering and to find a dose of tramadol that could provide the dual advantage of antishivering and analgesic effect in the postoperative period. The study included 165 patients, randomly allocated to five groups of 33 each. Tramadol in doses of 1, 2 and 3 mg.kg−1, pethidine 0.5 mg.kg−1 or normal saline were administered at the time of wound closure. All three doses of tramadol were effective and comparable to pethidine in preventing postanaesthetic shivering. Tramadol 2 mg.kg−1 had the best combination of antishivering and analgesic efficacy without excessive sedation and thus appeared to be a good choice to be administered at the time of wound closure to provide antishivering effect and analgesia without significant side effects in the postoperative period.
Tolerability, pharmacokinetics and night‐time effects on postural sway and critical flicker fusion of gaboxadol and zolpidem in elderly subjects
Authors: Boyle Julia , Danjou Philippe , Alexander Robert , Calder Nicole , Gargano Cynthia , Agrawal Nancy , Fu Irong , McCrea Jacqueline B. , Murphy M. Gail 
Published: December 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Body sway increases in older adults and may lead to an increase in the risk of falling.• The problem of impaired stability in the elderly may be compounded by the use of hypnotics, which have been associated with an increased risk of next‐day falls as well as drowsiness.• The potential adverse effects of hypnotic drugs on steadiness may be exacerbated during the night, in the event that an individual needs to get out of bed. WHAT THIS STUDY ADDS • This study examines the effects of gaboxadol (an investigational treatment for insomnia), zolpidem (a current hypnotic included as an active control) and placebo on body sway and attention/information processing ability following bedtime dosing in elderly subjects who were woken during the night for assessments.• Zolpidem and gaboxadol increased body sway at various time points during the night relative to placebo; at 1.5 h post dose, the time of peak concentrations of both drugs, gaboxadol produced less impairment than zolpidem.• Compared with placebo, neither gaboxadol nor zolpidem impaired attention/information‐processing ability as assessed by critical flicker fusion.AIMSTo evaluate tolerability, pharmacokinetics and night‐time effects on body sway and critical flicker fusion (CFF) of gaboxadol following bedtime dosing in healthy elderly subjects.METHODSSubjects (17 women, seven men) aged 65–75 years received gaboxadol 10 mg, zolpidem 5 mg (active control) or placebo at 22.00 h in a three‐period, randomized, double‐blind crossover study. They were awakened during the night for evaluation of body sway and CFF. Pharmacokinetics of gaboxadol were assessed during a fourth single‐blind treatment period. Adverse events were recorded throughout the study.RESULTSThe number of subjects with adverse events was 14 for gaboxadol 10 mg, seven for zolpidem and nine for placebo; most were mild or moderate in intensity. Two women discontinued the study following gaboxadol; one vomited and one experienced a severe vasovagal syncope after venepuncture. Mean gaboxadol tmax was 2 h, t½ was 1.7 h, AUC0–∞ was 430 ng·h ml−1 and Cmax was 139 ng ml−1. At 1.5 h and 4 h post dose, zolpidem increased body sway relative to placebo (P < 0.01). Gaboxadol increased body sway at 4 h (P < 0.001) and 8 h (P < 0.05) relative to placebo. At 1.5 h, the time point closest to peak drug concentrations, zolpidem increased body sway compared with gaboxadol (P < 0.01). Gaboxadol and zolpidem had no effects on CFF vs. placebo.CONCLUSIONSA bedtime dose of gaboxadol 10 mg was generally well tolerated. Changes in body sway at 1.5 h after bedtime dosing were smaller with gaboxadol 10 mg than with zolpidem 5 mg, whereas changes were similar at 4 h for both treatments and returned to near baseline at 8 h.
Influence of domperidone on pharmacokinetics, safety and tolerability of the dopamine agonist rotigotine
Authors: Braun Marina , Cawello Willi , Boekens Hilmar , Horstmann Rolf 
Published: December 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Rotigotine transdermal patch is a new non‐ergolinic dopamine agonist developed for the treatment of Parkinson's disease and restless legs syndrome.• Peripheral dopaminergic side‐effects of dopamine agonists such as nausea and vomiting can be prevented by the antiemetic agent domperidone. WHAT THIS STUDY ADDS • The study results show no evidence for an interaction of domperidone on bioavailability and steady‐state pharmacokinetics of transdermal rotigotine.• Co‐administration of domperidone and rotigotine does not require dose adjustments for rotigotine transdermal patch.AIMSTo evaluate the influence of the antiemetic agent domperidone on steady‐state pharmacokinetics, safety and tolerability of multiple‐dose treatment of the transdermally applied non‐ergolinic dopamine agonist rotigotine.METHODSSixteen healthy male subjects (mean age 30.3 years) participated in a randomized, two‐way crossover clinical trial. Treatment A consisted of transdermal rotigotine patch (2 mg (24 h)−1, 10 cm2, total drug content 4.5 mg) applied daily for 4 days, and concomitant oral domperidone (10 mg t.i.d.) for 5 days. For treatment B, subjects received only transdermal rotigotine treatment (daily for 4 days). Pharmacokinetic variables describing systemic exposure and renal elimination of rotigotine and metabolites, and safety and tolerability of the treatment were assessed.RESULTSThe primary steady‐state pharmacokinetic parameters (Cmax,ss and AUC(0–24),ss) were similar with or without co‐administration of domperidone. Geometric mean ratios were close to 1 and respective 90% confidence intervals were within the acceptance range of bioequivalence (0.8, 1.25): Cmax,ss 0.96 (0.86, 1.08) and AUC(0–24),ss 0.97 (0.87, 1.08). tmax,ss, t1/2, secondary parameters calculated on days 4/5 after repeated patch application (Cmin,ss, Cave,ss, AUC(0–tz)) and renal elimination for unconjugated rotigotine and its metabolites were also similar with and without comedication of domperidone. A reduction in the dopaminergic side‐effect nausea was seen with domperidone comedication.CONCLUSIONSNo changes of pharmacokinetic parameters describing systemic exposure and renal elimination of rotigotine were observed when domperidone was administered concomitantly with rotigotine. The lack of pharmacokinetic interactions indicates that a dose adjustment of rotigotine transdermal patch is not necessary with concomitant use of domperidone.
A color‐coded orthotopic nude‐mouse treatment model of brain‐metastatic paralyzing spinal cord cancer that induces angiogenesis and neurogenesis
Authors: Hayashi K.  , Yamauchi K.  , Yamamoto N.  , Tsuchiya H.  , Tomita K.  , Bouvet M.  , Wessels J.  , Hoffman R. M.  
Published: December 2008

AbstractObjective: Cancer of the spinal cord is highly malignant and often leads to paralysis and death. A realistic mouse model would be an important benefit for the better understanding and treatment of spinal cord glioma.Materials and methods: To develop an imageable, patient‐like model of this disease, U87 human glioma tumour fragments (expressing red fluorescent protein), were transplanted by surgical orthotopic implantation into the spinal cord of nontransgenic nude mice or transgenic nude mice expressing nestin‐driven green fluorescent protein (ND‐GFP). In ND‐GFP mice, GFP is expressed in nascent blood vessels and neural stem cells. The animals were treated with temozolomide or vehicle control.Results: The intramedullary spinal cord tumour grew at the primary site, caused hind‐limb paralysis and also metastasized to the brain. Temozolomide inhibited tumour growth (P < 0.01) and prevented metastasis, as well as prevented paralysis in four mice and delayed paralysis in two mice of the six tested (P = 0.005). In the ND‐GFP‐expressing host, ND‐GFP cells staining positively for neuronal class III‐β‐tubulin or CD31, surrounded the tumour. These results suggest that the tumour stimulated both neurogenesis and angiogenesis, respectively.Conclusion: A patient‐like model of spinal cord glioma was thus developed, which can be used for the discovery of new agents, including those that inhibit invasion and metastasis of the disease as well as those that prevent paralysis.
Homozygous nonsense and frameshift mutations of the ACTH receptor in children with familial glucocorticoid deficiency (FGD) are not associated with long‐term mineralocorticoid deficiency
Authors: Chan Li F. , Metherell Louise A. , Krude Heiko , Ball Colin , O'Riordan Stephen M. P. , Costigan Colm , Lynch Sally A. , Savage Martin O. , Cavarzere Paolo , Clark Adrian J. L. 
Published: December 2008

SummaryObjective  Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease characterized by isolated glucocorticoid deficiency with preserved mineralocorticoid secretion. Mutations in the ACTH receptor (MC2R) account for approximately 25% of all FGD cases, but since these are usually missense mutations, a degree of receptor function is frequently retained. A recent report, however, suggested that disturbances in the renin–aldosterone axis were seen in some patients with potentially more severe MC2R mutations. Furthermore, MC2R knock out mice have overt aldosterone deficiency and hyperkalaemia despite preservation of a normal zona glomerulosa. We wished to determine whether a group of patients with severe nonsense mutations of the MC2R exhibited evidence of mineralocorticoid deficiency, thereby challenging the conventional diagnostic feature of FGD which might result in diagnostic misclassification.Design  Clinical review of patients with nonsense MC2R mutations.Patients  Between 1993 and 2008, 164 patients with FGD were screened for mutations in the MC2R. Totally 42 patients (34 families) were found to have mutations in the MC2R. Of these, 6 patients (4 families) were found to have homozygous nonsense or frameshift mutations.Results  Mild disturbances in the renin–angiotensin–aldosterone axis were noted in four out of six patients, ranging from slightly elevated plasma renin levels to low aldosterone levels, although frank mineralocorticoid deficiency or electrolyte disturbance were not found. No patient required fludrocortisone replacement.Conclusion  Severe nonsense and frameshift MC2R mutations are not associated with clinically significant mineralocorticoid deficiency and are thus unlikely to require long‐term mineralocorticoid replacement.
Clinical value of the first automated TSH receptor autoantibody assay for the diagnosis of Graves’ disease (GD): an international multicentre trial
Authors: Schott Matthias , Hermsen Derik , Broecker‐Preuss Martina , Casati Marco , Mas Jordi Camara , Eckstein Anja , Gassner Dieter , Golla Ruth , Graeber Claudia , Van Helden Josef , Inomata Keiko , Jarausch Jochen , Kratzsch Jürgen , Miyazaki Naoko , Moreno Miguel Angel Navarro , Murakami Tsukasa , Roth Heinz Jürgen , Stock Werner , Noh Jaeduk Yoshimura , Scherbaum Werner A. , Mann Klaus 
Published: December 2008

SummaryBackground  Most recently, a new rapid and fully automated electrochemiluminescence immunoassay for the determination of TSH receptor autoantibodies (TRAb) based on the ability of TRAb to inhibit the binding of a human thyroid‐stimulating monoclonal antibody (M22) has been established.Objective  To evaluate this assay system in clinical routine based on an international multicentre trial and to compare the results with other established TRAb assays.Patients and measurements  Totally 508 Graves’ disease (GD), 142 autoimmune thyroiditis, 107 subacute thyroiditis, 109 nonautoimmune nodular goitre, 23 thyroid cancer patients and 446 normal controls were retrospectively evaluated.Results  ROC plot analysis revealed an area under curve of 0·99 (95% CI: 0·99–1·0) indicating a high assay sensitivity and specificity. The highest sensitivity (99%) and specificity (99%) was seen at a cut‐off level of 1·75 IU/l. Here, the calculated positive predictive value was 95%, whereas the negative predictive value was 100%. Applying the ROC plot‐derived cut‐off of 1·75 IU/l we found a sensitivity for TRAb positivity within the group of newly diagnosed GD patients of 97% which is in accordance to the sum of different nonautomated porcine TSH receptor‐based assays with a sensitivity of 94% indicating an excellent analytical performance of the new assay format. Detailed comparison of the automated and the sum of manual assays revealed a near identical specificity.Conclusion  Our results demonstrate that this new assay system has a high sensitivity for detecting GD and specificity for discriminating from other thyroid diseases. This assay may represent the future technology for rapid fully automated TRAb detection.
Quality of life in children and adolescents 1‐year after cure of Cushing syndrome: a prospective study
Authors: Keil Margaret F. , Merke Deborah P. , Gandhi Roma , Wiggs Edythe A. , Obunse Kathy , Stratakis Constantine A. 
Published: December 2008

SummaryObjective  Cushing syndrome (CS) in children is associated with symptoms that may impair health related quality of life (HRQL). There are no prospective reports of HRQL in children with CS.Methods  Prospective study of 40 children (mean age 13 ± 3·2 years) with CS evaluated prior to and 1‐year post‐treatment. The Child Health Questionnaire (CHQ) was used to assess HRQL; Wechsler Intelligence Scale for Children (WASI) was used to assess cognitive function, and patient‐reported symptoms were assessed with a CS symptom checklist.Results  Active CS was associated with low physical and psychosocial summary scores compared to US population data (P < 0·001). Despite improvement from pre‐ to 1‐year postcure, residual impairment remained in physical summary and function, and role‐physical, global health and emotional impact (parent) scores. Incomplete recovery of adrenal function at 1‐year post‐treatment was associated with impaired scores. WASI IQ scores declined and a correlation was noted between age at first evaluation and IQ score changes. Most self‐reported CS symptoms showed improvement, but forgetfulness, unclear thinking and decreased attention span did not improve after cure of CS.Conclusion  CS in children and adolescents is associated with impaired HRQL, with residual impairment 1 year after cure. Our results also suggest that younger children are more likely to experience negative changes in cognitive function. HRQL is an important outcome measure in children and adolescents with CS and identification of factors that contribute to HRQL may help to diminish the physical and psychological burden of disease in this population of patients.
New advances in regularized inversion of gravity and electromagnetic data
Authors: Zhdanov Michael S. 
Published: December 2008

ABSTRACTThe interpretation of potential and electromagnetic fields observed over 3D geological structures remains one of the most challenging problems of exploration geophysics. In this paper I present an overview of novel methods of inversion and imaging of gravity and electromagnetic data, which are based on new advances in the regularization theory related to the application of special stabilizing functionals, which allow the reconstruction of both smooth images of the underground geological structures and models with sharp geological boundaries. I demonstrate that sharp‐boundary geophysical inversion can improve the efficiency and resolution of the inverse problem solution. The methods are illustrated with synthetic and practical examples of the 3D inversion of potential and electromagnetic field data.
Regulation of different inflammatory diseases by impacting the mevalonate pathway
Authors: Zeiser Robert , Maas Kristina , Youssef Sawsan , Dürr Christoph , Steinman Lawrence , Negrin Robert S. 
Published: December 2008

SummaryThe 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A reductase inhibitors (statins) interfere with the mevalonate pathway. While initially developed for their lipid‐lowering properties, statins have been extensively investigated with respect to their impact on autoantigen and alloantigen driven immune responses. Mechanistically it was shown that statins modify immune responses on several levels, including effects on dendritic cells, endothelial cells, macrophages, B cells and T cells. Several lines of evidence suggest that statins act in a disease‐specific manner and are not effective in each immune disorder. This review discusses possible modes of action of statins in modulating immunity towards autoantigens and alloantigens.
Epigenetics and T helper 1 differentiation
Authors: Aune Thomas M. , Collins Patrick L. , Chang Shaojing 
Published: December 2008

SummaryNaïve T helper cells differentiate into two subsets, T helper 1 and 2, which either transcribe the Ifng gene and silence the Il4 gene or transcribe the Il4 gene and silence the Ifng gene, respectively. This process is an essential feature of the adaptive immune response to a pathogen and the development of long‐lasting immunity. The ‘histone code’ hypothesis proposes that formation of stable epigenetic histone marks at a gene locus that activate or repress transcription is essential for cell fate determinations, such as T helper 1/T helper 2 cell fate decisions. Activation and silencing of the Ifng gene are achieved through the creation of stable epigenetic histone marks spanning a region of genomic DNA over 20 times greater than the gene itself. Key transcription factors that drive the T helper 1 lineage decision, signal transducer and activator 4 (STAT4) and T‐box expressed in T cells (T‐bet), play direct roles in the formation of activating histone marks at the Ifng locus. Conversely, STAT6 and GATA binding protein 3, transcription factors essential for the T helper 2 cell lineage decision, establish repressive histone marks at the Ifng locus. Functional studies demonstrate that multiple genomic elements up to 50 kilobases from Ifng play critical roles in its proper transcriptional regulation. Studies of three‐dimensional chromatin conformation indicate that these distal regulatory elements may loop towards Ifng to regulate its transcription. We speculate that these complex mechanisms have evolved to tightly control levels of interferon‐γ production, given that too little or too much production would be very deleterious to the host.
Assessment of pulp vitality: a review
Authors: GOPIKRISHNA VELAYUTHAM , PRADEEP GALI , VENKATESHBABU NAGENDRABABU 
Published: December 2008

Background.  One of the greatest diagnostic challenges in clinical practice is the accurate assessment of pulp status. This may be further complicated in paediatric dentistry where the practitioner is faced with a developing dentition, traumatized teeth, or young children who have a limited ability to recall a pain history for the tooth in question. A variety of pulp testing approaches exist, and there may be confusion as to their validity or appropriateness in different clinical situations.Aim.  The aim of this paper is to provide the clinician with a comprehensive review of current pulp testing methods. A key objective is to highlight the difference between sensitivity testing and vitality testing. A biological basis for pulp testing is also provided to allow greater insight into the interpretation of pulp testing results. The rationale for, and methods of, assessing pulpal blood flow are described.
Histological comparison of pulpal inflammation in primary teeth with occlusal or proximal caries
Authors: KASSA DESPOINA , DAY PETER , HIGH ALEX , DUGGAL MONTY 
Published: December 2008

Objective.  A number of clinical and histological studies have investigated caries‐related changes in the primary tooth pulp, but the effect of caries site, as a clinical variable, has not been previously considered. This study sought to compare inflammatory changes within the pulp of primary molars according to the location of the caries lesion (occlusal or proximal).Methods.  Eighty‐three primary molars were extracted under general anaesthesia for caries and/or orthodontic reasons, and were split immediately after removal and fixed in 10% formalin. Teeth were then decalcified, sectioned, and stained with haematoxylin and eosin for histological examination using light microscopy. Caries depth was measured using a graticle, and the site of the caries lesion noted as occlusal or proximal. Samples were further classified into one of five subgroups according to the observed degree of pulpal inflammation.Results.  Key findings were that where caries depth was less than 50% of the total dentine thickness, there were no significant differences in inflammatory status according to caries site. In contrast, marked inflammatory changes were significantly more likely throughout the coronal pulp of teeth with proximal caries compared to teeth with occlusal caries where caries depth was equal to, or greater than, 50% of the total dentine thickness (P = 0.017, Fisher's exact test).Conclusion.  Primary teeth with proximal carious lesions extending more than 50% through the dentine thickness appear to have more extensive inflammatory pulpal changes than teeth with occlusal caries of a similar depth. This finding has clinical implications and may help inform treatment decisions in the management of primary teeth with deep carious lesions.
Pulpal status of human primary teeth with physiological root resorption
Authors: MONTEIRO JOANA , DAY PETER , DUGGAL MONTY , MORGAN CLAIRE , RODD HELEN 
Published: December 2008

Objective.  The overall aim of this study was to determine whether any changes occur in the pulpal structure of human primary teeth in association with physiological root resorption.Methods.  The experimental material comprised 64 sound primary molars, obtained from children requiring routine dental extractions under general anaesthesia. Pulp sections were processed for indirect immunofluorescence using combinations of: (i) protein gene product 9.5 (a general neuronal marker); (ii) leucocyte common antigen CD45 (a general immune cell marker); and (iii) Ulex europaeus I lectin (a marker of vascular endothelium). Image analysis was then used to determine the percentage area of staining for each label within both the pulp horn and mid‐coronal region. Following measurement of the greatest degree of root resorption in each sample, teeth were subdivided into three groups: those with physiological resorption involving less than one‐third, one‐third to two‐thirds, and more than two‐thirds of their root length.Results.  Wide variation was evident between different tooth samples with some resorbed teeth showing marked changes in pulpal histology. Decreased innervation density, increased immune cell accumulation, and increased vascularity were evident in some teeth with advanced root resorption. Analysis of pooled data, however, did not reveal any significant differences in mean percentage area of staining for any of these variables according to the three root resorption subgroups (P > 0.05, analysis of variance on transformed data).Conclusions.  This investigation has revealed some changes in pulpal status of human primary teeth with physiological root resorption. These were not, however, as profound as one may have anticipated. It is therefore speculated that teeth could retain the potential for sensation, healing, and repair until advanced stages of root resorption.