bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experience Is Not Enough
Authors: Friedman Zeev , Siddiqui Naveed , Katznelson Rita , Devito Isabella , Davies Sharon 
Published: April 2008

Background
Invasive procedures such as epidural anesthesia carry risks for complications such as erroneous placement arising from inadequate manual skills and infection secondary to breaches in aseptic technique. Although it is assumed that improvement in aseptic technique parallels improved dexterity, this assertion remains unproven. The aim of this study was to determine whether increased proficiency in the manual skills for epidural anesthesia is associated with improved aseptic technique.

Methods
Second-year anesthesia residents were repeatedly videotaped performing epidural anesthesia over 6-month periods. Three independent examiners blinded to the level of training of the residents evaluated the procedures for manual skills and aseptic technique. Each procedure was graded using a manual skills checklist, a global rating scale, and an aseptic technique checklist. The main outcome measures were the scores for these three tools.

Results
Thirty-five sessions were videotaped over 1 yr. Interrater reliability was nearly perfect. A strong positive association was found between increased experience and manual skills, as reflected by the scores achieved on both the manual skills checklist and the global rating scale. In contrast, a nonsignificant or very weak correlation was found between the aseptic technique checklist total scores and the number of epidurals performed.

Conclusion
Manual skills for invasive procedures improved with increasing experience, but aseptic technique did not, despite formal teaching. These findings reflect major gaps in the understanding and teaching of the principles of aseptic technique, most likely due to lack of structured training. Educational initiatives are needed to correct these teaching gaps.
Local Myotoxicity from Sustained Release of Bupivacaine from Microparticles
Authors: Padera Robert , Bellas Evangelia , Tse Julie Y. , Hao Daphne , Kohane Daniel S. 
Published: April 2008

Background
Sustained release of local anesthetics is frequently associated with myotoxicity. The authors investigated the role of particulate delivery systems and of the pattern of drug release in causing myotoxicity.

Methods
Rats were given sciatic nerve blocks with bupivacaine solutions, two types of bupivacaine-containing microparticles (polymeric microspheres and lipid-protein-sugar particles), or blank particles with or without bupivacaine in the carrier fluid. Myotoxicity was scored in histologic sections of the injection sites. Bupivacaine release kinetics from the particles were measured. Myotoxicity of a range of bupivacaine concentrations from exposures up to 3 weeks was assessed in C2C12 myotubes, with or without microparticles.

Results
Both types of bupivacaine-loaded microparticles, but not blank particles, were associated with myotoxicity. Whereas 0.5% bupivacaine solution caused little myotoxicity, a concentration of bupivacaine that mimicked the amount of bupivacaine released initially from particles caused myotoxicity. Local anesthetics showed both concentration and time-dependent myotoxicity in C2C12s. Importantly, even very low concentrations that were nontoxic over brief exposures became highly toxic after days or weeks of exposure. The presence of particles did not increase bupivacaine myotoxicity in vitro but did in vivo. Findings applied to both particle types.

Conclusions
Whereas the release vehicles themselves were not myotoxic, both burst and extended release of bupivacaine were. A possible implication of the latter finding is that myotoxicity is an inevitable concomitant of sustained release of local anesthetics. Particles, and perhaps other vehicles, may enhance local toxicity through indirect mechanisms.
Differential Effects of Isoflurane and Propofol on Upper Airway Dilator Muscle Activity and Breathing
Authors: Eikermann Matthias , Malhotra Atul , Fassbender Philipp , Zaremba Sebastian , Jordan Amy S. , Gautam Shiva , White David P. , Chamberlin Nancy L. 
Published: April 2008

Background
Anesthesia impairs upper airway integrity, but recent data suggest that low doses of some anesthetics increase upper airway dilator muscle activity, an apparent paradox. The authors sought to understand which anesthetics increase or decrease upper airway dilator muscle activity and to study the mechanisms mediating the effect.

Methods
The authors recorded genioglossus electromyogram, breathing, arterial blood pressure, and expiratory carbon dioxide in 58 spontaneously breathing rats at an estimated ED50 (median effective dose) of isoflurane or propofol. The authors further evaluated the dose-response relations of isoflurane under different study conditions: (1) normalization of mean arterial pressure, or end-expiratory carbon dioxide; (2) bilateral lesion of the Kölliker-Fuse nucleus; and (3) vagotomy. To evaluate whether the markedly lower inspiratory genioglossus activity during propofol could be recovered by increasing flow rate, a measure of respiratory drive, the authors performed an additional set of experiments during hypoxia or hypercapnia.

Results
In vagally intact rats, tonic and phasic genioglossus activity were markedly higher with isoflurane compared with propofol. Both anesthetics abolished the genioglossus negative pressure reflex. Inspiratory flow rate and anesthetic agent predicted independently phasic genioglossus activity. Isoflurane dose-dependently decreased tonic and increased phasic genioglossus activity, and increased flow rate, and its increasing effects were abolished after vagotomy. Impairment of phasic genioglossus activity during propofol anesthesia was reversed during evoked increase in respiratory drive.

Conclusion
Isoflurane compared with propofol anesthesia yields higher tonic and phasic genioglossus muscle activity. The level of respiratory depression rather than the level of effective anesthesia correlates closely with the airway dilator muscle function during anesthesia.
Glycine Transporter Inhibitors as a Potential Therapeutic Strategy for Chronic Pain with Memory Impairment
Authors: Tanabe Mitsuo , Takasu Keiko , Yamaguchi Sachiko , Kodama Daisuke , Ono Hideki 
Published: April 2008

Background
Impaired excitatory and inhibitory balance in the spinal dorsal horn has a crucial role in the pathophysiology of chronic pain. The authors addressed the therapeutic impact of increasing spinal glycine applied exogenously or via blockade of glycine transporter 1 using its selective inhibitors sarcosine and N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine on neuropathic and inflammatory pain in mice.

Methods
Mice with thermal and mechanical hypersensitivity after partial ligation of the sciatic nerve (Seltzer model) or mice with mechanical hypersensitivity after streptozotocin injection received intrathecal injection of glycine, sarcosine, and N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine. These drugs were also intrathecally injected in mice to assess their effects on formalin-evoked nociceptive behaviors. The supraspinal effect of blockade of glycine transporter 1 was studied on tetanus-induced long-term potentiation of the Schaffer-collateral synapses in hippocampal slices prepared from Seltzer model mice.

Results
Glycine, sarcosine, and N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine ameliorated thermal and mechanical hypersensitivity in Seltzer model mice, and reduced mechanical hypersensitivity in streptozotocin-injected diabetic mice. Moreover, they selectively inhibited the second phase of formalin-evoked licking/biting behavior. In hippocampal slices prepared from Seltzer model mice, long-term potentiation was maintained at a significantly lower level than that in sham-treated mice. Such impairment of long-term potentiation was never observed when it was induced in the presence of N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine.

Conclusions
An increase in endogenous glycine via glycine transporter 1 blockade not only results in a net inhibitory influence on pain transmission at the spinal level but also supraspinally relieves decreased synaptic efficacy presumably related to cognitive disturbance often described in patients with chronic pain.
Extravascular papillary endothelial hyperplasia of the palm masquerading as an angiosarcoma
Authors: ARAI Eiichi , SHIMIZU Michio , OGAWA Fumihiro , HIROSE Takanori , OHBAYASHI Hiroto , TAGUCHI Satoshi , TSUCHIDA Tetsuya 
Published: April 2008

ABSTRACTCutaneous extravascular papillary endothelial hyperplasia (PEH) is a rare lesion presenting as a cutaneous mass and histologically mimicking angiosarcoma. Herein, we describe a patient who presented with a palm tumor that had developed after trauma. Histologically, the lesion was ulcerated and showed proliferation of atypical epithelioid cells with nuclear enlargement and mitosis. Vascular proliferation was evident, and these were positive for CD31 and CD34, with approximately 20% positivity for MIB‐1. We diagnosed this case as an extravascular papillary endothelial hyperplasia because there was no evidence of invasion into the surrounding tissue and elastica staining proved it did not have a vascular structure. To our knowledge, cutaneous extravascular PEH has not yet been reported in the published work.
A developmental approach to alcohol drinking behaviour in adulthood: a follow‐up study from age 8 to age 42
Authors: Pitkänen Tuuli , Kokko Katja , Lyyra Anna‐Liisa , Pulkkinen Lea 
Published: April 2008

ABSTRACTAims  To study the links of family background, child and adolescent social behaviour, and (mal)adaptation with heavy drinking by age 20 and with the frequency of drinking, binge drinking, Cut‐down, Annoyed, Guilt, Eye‐opener (CAGE) questionnaire scores and problems due to drinking at ages 27 and 42 years.Design  In the Finnish Jyväskylä Longitudinal Study of Personality and Social Development, data have been collected by interviews, inventories and questionnaires. Behavioural data were gathered at ages 8 and 14; data on alcohol consumption were gathered at ages 14, 20, 27, 36 and 42.Participants  A total of 184 males and 163 females; 94% of the original sample of the 8‐year‐olds.Findings  Family adversities, externalizing problem behaviours, low school success, truancy and substance use in adolescence were associated in early middle age with problems due to drinking in both genders, and to binge drinking and CAGE scores in females. The antecedents varied, however, across the indicators of drinking and gender. The frequency of drinking was least predictable by the studied antecedents. Childhood and adolescent antecedents and drinking up to age 20 explained 43% of males' and 31% of females' problem drinking at age 42; 31% and 19%, respectively, at age 27.Conclusions  The early warning signs of drinking problems should be taken seriously in the preventive work for alcohol abuse. Problem drinking in early middle age is preceded by maladjustment to school, early age of onset of drinking and heavy drinking in adolescence even more significantly than problem drinking in early adulthood.
Adolescent pathways to adulthood drinking: sport activity involvement is not necessarily risky or protective
Authors: Peck Stephen C. , Vida Mina , Eccles Jacquelynne S. 
Published: April 2008

ABSTRACTAims  Use pattern‐centered methods to examine how adolescents' alcohol use and sports activities are related both to childhood sport and problem behavior and to heavy drinking in early adulthood.Design  The data used in this study come from four waves of the Michigan Study of Adolescent Life Transitions (MSALT) that began in 1983, when participants were approximately age 12, and continued into early adulthood, when participants were approximately age 28.Participants  Sixty per cent of the approximately 1000 MSALT youth living in south‐eastern Michigan were females and 97% were European American. Approximately 28% of one or both parents held at least a college degree, and 45% held a high school diploma or lower.Findings  Pattern‐centered analyses revealed that the relation between adolescent sport activity and age 28 heavy alcohol use obtained primarily for sport participants who were also using more than the average amount of alcohol and other drugs at age 18. Similarly, children who were characterized by relatively high levels of sport participation, aggression and other problem behavior at age 12 were more likely than expected by chance to become sport participants who used more than the average amount of alcohol and other drugs at age 18.Conclusions  The results indicate that childhood problem behavior and adolescent sport participation can, but do not necessarily, presage heavy drinking in adulthood and that pattern‐centered analytical techniques are useful for revealing such theoretically generated predictions.
Indole‐3‐acetic acid (IAA) biosynthesis in the smut fungus Ustilago maydis and its relevance for increased IAA levels in infected tissue and host tumour formation
Authors: REINEKE GAVIN , HEINZE BERNADETTE , SCHIRAWSKI JAN , BUETTNER HERMANN , KAHMANN REGINE , BASSE CHRISTOPH W. 
Published: April 2008

SUMMARYInfection of maize (Zea mays) plants with the smut fungus Ustilago maydis is characterized by excessive host tumour formation. U. maydis is able to produce indole‐3‐acetic acid (IAA) efficiently from tryptophan. To assess a possible connection to the induction of host tumours, we investigated the pathways leading to fungal IAA biosynthesis. Besides the previously identified iad1 gene, we identified a second indole‐3‐acetaldehyde dehydrogenase gene, iad2. Δiad1Δiad2 mutants were blocked in the conversion of both indole‐3‐acetaldehyde and tryptamine to IAA, although the reduction in IAA formation from tryptophan was not significantly different from Δiad1 mutants. To assess an influence of indole‐3‐pyruvic acid on IAA formation, we deleted the aromatic amino acid aminotransferase genes tam1 and tam2 in Δiad1Δiad2 mutants. This revealed a further reduction in IAA levels by five‐ and tenfold in mutant strains harbouring theΔtam1 andΔtam1Δtam2 deletions, respectively. This illustrates that indole‐3‐pyruvic acid serves as an efficient precursor for IAA formation in U. maydis. Interestingly, the rise in host IAA levels upon U. maydis infection was significantly reduced in tissue infected with Δiad1Δiad2Δtam1 orΔiad1Δiad2Δtam1Δtam2 mutants, whereas induction of tumours was not compromised. Together, these results indicate that fungal IAA production critically contributes to IAA levels in infected tissue, but this is apparently not important for triggering host tumour formation.
Plant programmed cell death: can't live with it; can't live without it
Authors: WILLIAMS BRETT , DICKMAN MARTY 
Published: April 2008

SUMMARYThe decision of whether a cell should live or die is fundamental for the wellbeing of all organisms. Despite intense investigation into cell growth and proliferation, only recently has the essential and equally important idea that cells control/programme their own demise for proper maintenance of cellular homeostasis gained recognition. Furthermore, even though research into programmed cell death (PCD) has been an extremely active area of research there are significant gaps in our understanding of the process in plants. In this review, we discuss PCD during plant development and pathogenesis, and compare/contrast this with mammalian apoptosis.
Expression of a bacterial flagellin gene triggers plant immune responses and confers disease resistance in transgenic rice plants
Authors: TAKAKURA YOSHIMITSU , CHE FANG‐SIK , ISHIDA YUJI , TSUTSUMI FUMIKI , KUROTANI KEN‐ICHI , USAMI SATORU , ISOGAI AKIRA , IMASEKI HIDEMASA 
Published: April 2008

SUMMARYFlagellin is a component of bacterial flagella and acts as a proteinaceous elicitor of defence responses in organisms. Flagellin from a phytopathogenic bacterium, Acidovorax avenae strain N1141, induces immune responses in suspension‐cultured rice cells. To analyse the function of flagellin in rice, we fused the N1141 flagellin gene to the cauliflower mosaic virus 35S promoter and introduced it into rice. Many of the resulting transgenic rice plants accumulated flagellin at various levels. The transgenic rice developed pale spots in the leaves. The expression of a defence‐related gene for phenylalanine ammonia‐lyase was induced in the transgenic plants, and H2O2 production and cell death were observed in some plants with high levels of gene expression, suggesting that the flagellin triggers immune responses in the transgenic rice. Transgenic plants inoculated with Magnaporthe grisea, the causal agent of rice blast, showed enhanced resistance to blast, suggesting that the flagellin production confers disease resistance in the transgenic rice.
Cost‐utility analysis of Canadian tailored prophylaxis, primary prophylaxis and on‐demand therapy in young children with severe haemophilia A
Authors: RISEBROUGH N. , OH P. , BLANCHETTE V. , CURTIN J. , HITZLER J. , FELDMAN B. M. 
Published: April 2008

Summary. Primary prophylaxis is the emerging standard treatment for boys with severe haemophilia. Tailored (escalating‐dose) prophylaxis (EscDose), beginning at a low frequency and escalating with repeated bleeding may prevent arthropathy at a lower cost than standard prophylaxis (SP). From a societal perspective, we compared the incremental cost per joint‐haemorrhage that is avoided and quality‐adjusted‐life‐year (QALY) gained of SP and EscDose to on‐demand (Demand) therapy in severe haemophilia A boys treated to age 6 using a decision analytic model. Costs included factor VIII (FVIII), professional visits and tests, central venous placement/complications, hospitalization, home programmes and parents’ lost work‐days. Resource utilization was estimated by surveying 17 Canadian clinics. The natural history of bleeding and other probabilities were determined from a longitudinal chart review (n = 24) and published literature. EscDose costs an additional $3192 per joint‐haemorrhage that was avoided compared with Demand whereas SP costs an additional $9046 per joint‐haemorrhage that was avoided compared with EscDose. Clinic costs and lost wages were reduced by 60–80% for EscDose and SP compared with Demand. EscDose attained more QALYs than SP and Demand on account of less bleeding than Demand and lower need for ports than SP. The incremental cost per QALY for EscDose vs. Demand was $542 938. EscDose was less expensive with similar QALYs compared to SP. Sensitivity analysis was performed on all probability‐ and cost‐estimates, and showed the model was sensitive to the cost of FVIII and the SP and target joint utilities. In conclusion, prophylaxis will substantially improve clinical outcomes and quality of life compared to Demand treatment, but with substantial cost.
Single dose intravenous thioacetamide administration as a model of acute liver damage in rats
Authors: Chen Tse‐Min , Subeq Yi‐Maun , Lee Ru‐Ping , Chiou Tzyy‐Wen , Hsu Bang‐Gee 
Published: April 2008

SummaryThioacetamide (TAA) has been used extensively in the development of animal models of acute liver injury. Frequently, TAA is administered intraperitoneally to induce liver damage under anaesthesia. However, it is rarely administered by intravenous injection in conscious rats. The experiments in this study were designed to induce acute liver damage by single intravenous injection of TAA (0, 70 and 280 mg/kg) in unrestrained rats. Biochemical parameters and cytokines measured during the 60‐h period following TAA administration, included white blood cells (WBC), haemoglobulin (Hb), platelet, aspartate transferase (GOT), alanine transferase (GPT), total bilirubin (TBIL), direct bilirubin (DBI), albumin, ammonia (NH3), r‐glutamyl transpeptidase (r‐GT), tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). Rats were sacrificed by decapitation 60 h after TAA administration and livers were removed immediately for pathology and immunohistochemical (IHC) examination. Another group of rats were sacrificed by decapitation 1, 6 and 24 h after TAA administration and livers were removed immediately for time course change of pathology and IHC examination. TAA significantly increased blood WBC, GOT, GPT, TBIL, DBIL, NH3, r‐GT, TNF‐α and IL‐6 levels but decreased the blood Hb, platelet and albumin level. The levels of histopathological damage in the liver after intravenous TAA administration were also increased with a dose‐dependent trend and more increased at 60 h after TAA administration. The levels of inducible nitric oxide synthase (iNOS) and nuclear factor‐κB (NF‐κB) detected by IHC in the liver after intravenous TAA administration were also increased with a dose‐dependent trend and more increased at 1 h after TAA administration. Single intravenous TAA administration without anaesthesia is a restorable animal model which may be used to investigate acute liver damage.
A comparison of the knowledge of, experience with and attitudes towards complementary and alternative medicine between nurses and patients in Korea
Authors: Yom Young‐Hee , Lee Kyu Eun 
Published: April 2008

Aims and objectives.  To compare nurses’ and patients’ knowledge of, experience with and attitudes towards complementary and alternative medicine (CAM).Background.  Despite increasing interest in, and use of, CAM among the public and health care providers, research on CAM‐related nursing is limited. Furthermore, the level of knowledge and attitudes towards, and use of CAM between nurses and patients have never been studied in Korea. Therefore, a comparison is called for with regard to the knowledge, experience and attitudes of patients and nurses in Korea regarding CAM.Designs.  A cross‐sectional survey design was used.Methods.  A convenience sample of 485 nurses and 367 patients responded to three questionnaires covering issues including their knowledge levels, attitudes towards and their use of CAM. Data were analysed using descriptive and inferential statistics.Results.  Overall, nurses had significantly higher mean scores in their knowledge of CAM than patients. Most nurses and patients had heard about CAM, but few had sufficient knowledge to perform CAM. Nurses had more education, experience and positive attitudes regarding CAM than patients.Conclusions.  Nurses need to be knowledgeable about CAM so that correct information and support can be provided to their patients.Relevance to clinical practice.  Nurses need additional training or education on CAM, because they should be able to respond adequately to questions from patients. Ultimately, nurses have an important role in helping patients use CAM safely.
Pharmacokinetics of kanamycin in dogs
Authors: BAGGOT J. DESMOND 
Published: April 2008

The pharmacokinetics of kanamycin were studied in beagle dogs. A parenteral preparation of kanamycin sulphate (5% aqueous solution), which was given at a dosage level of 10 mg/kg of body weight, was the drug product used. The disposition curve which resulted from the intravenous administration of a single bolus dose of the drug was completely described by the biexponential equation: C
p= 50e‐0.1977t+ 36.3e‐0.0128t where Cp represents concentration of the drug in the serum at time t (in minutes) and the experimental constants are mean values. Pseudo‐distribution equilibrium was rapidly attained and the apparent volumes of the central and peripheral compartments of the two‐compartment open model were the same (ca 125 ml/kg). Body clearance (mean ± S.D., n= 6) of kanamycin was 3.21 ±0.72 ml/kg/min. The half‐life of the drug was short (58.18 ± 18.43 min) and independent of the route of parenteral (intravenous and intramuscular) administration. Absorption of kanamycin from the intramuscular site was rapid, with a half‐time of 9.08 ± 1.10 min. A systemic availability of 89.1 ± 15.8% was obtained. Based on the bioavailability and disposition kinetics a dosage regimen consisting of the intramuscular injection of the dose (10 mg/kg) at 6 h intervals is proposed. An intravenous infusion rate of 48 μg/kgymin is predicted to establish a steady state serum concentration of 15 μg/ml, which is a therapeutic level of the antibiotic for susceptible micro‐organisms.