A randomised trial of peri-operative positive airway pressure for postoperative delirium in patients at risk for obstructive sleep apnoea after regional anaesthesia with sedation or general anaesthesia for joint arthroplasty.

Previous pilot work has established an association between obstructive sleep apnoea and the development of acute postoperative delirium , but it remains unclear to what extent this risk factor is modifiable in the 'real world' peri-operative setting. In a single-blind randomised controlled trial, 135 elderly surgical patients at risk for obstructive sleep apnoea were randomly assigned to receive peri-operative continuous positive airway pressure (CPAP) or routine care. Of the 114 patients who completed the study, 21 (18.4%) experienced delirium. Delirium was equally common in both groups: 21% (12 of 58 subjects) in the CPAP group and 16% (9 of 56 subjects) in the routine care group (OR = 1.36 [95%CI 0.52-3.54], p = 0.53). Delirious subjects were slightly older - mean (SD) age 68.9 (10.7) vs. 64.9 (8.2), p = 0.07 - but had nearly identical pre-operative STOP-Bang scores (4.19 (1.1) versus 4.27 (1.3), p = 0.79). Subjects in the CPAP group used their devices for a median (IQR [range]) of 3 (0.25-5 [0-12]) nights pre-operatively (2.9 (0.1-4.8 [0.0-12.7]) hours per night) and 1 (0-2 [0-2]) nights postoperatively (1.4 (0.0-5.1 [0.0-11.6]) hours per night). Among the CPAP subjects, the residual pre-operative apnoea-hypopnea index had a significant effect on delirium severity (p = 0.0002). Although we confirm that apnoea is associated with postoperative delirium, we did not find that providing a short-course of auto-titrating CPAP affected its likelihood or severity. Voluntary adherence to CPAP is particularly poor during the initiation of therapy.

Exploring the consistency, transparency and portability of dental technology education: benchmarking across Norway, Ireland and Australia.

Dental technology programmes of study must prepare students to practice in a broad range of contemporary workplaces. Currently, there is limited evidence to benchmark dental technology education - locally, nationally or internationally. This research aims to improve consistency, transparency and portability of dental technology qualifications across three countries. Data were accessed from open-source curriculum documents and five calibrated assessment items. Three institutions collaborated with Oslo and Akershus University College, Norway; Trinity College Dublin, Ireland; and Griffith University, Australia. From these, 29-44 students completed 174 assessments. The curricula reflect the community needs of each country and display common themes that underpin professional dental technology practice. Assessment results differed between institutions but no more than a normal distribution. Face-to-face assessment moderation was critical to achieve consistency. This collaborative research has led to the development of a set of guidelines for other dental technology education providers interested in developing or aligning courses internationally to enhance the portability of qualifications.

Interprofessional learning enhances knowledge of roles but is less able to shift attitudes: a case study from dental education.

INTRODUCTION: Interprofessional education (IPE) purports to improve team working through improved knowledge of the roles of others, and by engendering mutual respect. This case study aimed to determine the impact of an IPE curriculum on knowledge and attitudes of dentistry and dental technology students undertaking these curricula in the new School of Dentistry and Oral Health at Griffith University. All dental technology students and third- and final- (fifth) year dentistry students were invited to participate. METHOD: A mixed-method approach was used to compare attitudes, perceptions and experiences of students involved in our IPE curricula. Quantitative data were evaluated with the Statistical Package for the Social Sciences (SPSS), and qualitative findings were explored through an Excel(®) spreadsheet coding frame tested against Leximancer™ qualitative software for consistency. RESULTS: Forty-six of the 131 eligible students participated. Readiness for Interprofessional Learning Scales (RIPLS) and focus groups consistently showed that IPE positively influenced professional identity and improved communication between and amongst all students and assisted them in developing their roles. A prevailing sense of greater importance and a lack of mutual respect between dentistry and dental technology students were, unfortunately, evident. The process was, however, sufficient to enhance teamwork and collaboration when planned learning revolved around explicit patient care in the provision of dental prostheses. CONCLUSION: Further development of such curricula is needed to maximise IP learning (IPL) opportunities, to shift traditional attitudes and, potentially, to improve the outcomes of patient care. To enable this, academic and clinical leaders need to embrace the ideals of IPE.

An exploratory study of perfectionism, professional factors and psychological well-being of dentistry academics.

BACKGROUND: Well-being might be lower among dentistry professionals than other health professionals, and differ by personal, professional and sociodemographic factors. Few studies have considered dentistry academics who have different work roles and functions than clinicians. This exploratory study focused on well-being among dentistry academics and aimed to explore associations with perfectionism, professional factors and sociodemographics. METHOD: An online survey was carried out with academic staff in Dentistry and Oral Health departments of nine Universities in Australia and New Zealand. Well-being was assessed using the 22-item Psychological General Well-Being Index, with a maximum score of 110 indicating good well-being. Perfectionism was assessed using the 8-item Short Almost Perfect Scale, with a maximum score of 56 and a higher score indicating perfectionism. Twenty items were used to assess professional and 7 items assessed sociodemographic factors. Associations were explored using correlation and multiple linear regression. RESULTS: There was no significant bivariate association between perfectionism and well-being. Multiple linear regression indicated a significant association between hours of undergraduate teaching and psychological well-being, after adjustment for age, gender, income and overall health. CONCLUSION: This exploratory study showed poor well-being among dentistry academics, particularly in those teaching undergraduate students for more than 6 h/week.

Functional analysis of c-Myb protein in T-lymphocytic cell lines shows that it trans-activates the c-myc promoter.

The function of c-Myb protein was revealed by transfecting an expression vector containing the entire c-Myb protein-coding sequence into the murine CTLL-2 T-cell line. Expressions of high levels of c-Myb protein did not alter the expression of several T-cell markers, c-fos mRNA expression, responses to interleukin-2, and growth characteristics of these cells. Interestingly, expression of the c-myc gene was drastically increased in this clone. Further, the c-myb expression plasmid, but not a frameshift mutant of c-myb, enhanced the expression of a hybrid construct of c-myc promoter linked to a reporter gene by 8- to 14-fold. These results demonstrate a role of c-Myb protein in c-myc gene expression.

Evidence for an early degradative event to the insulin molecule following binding to hepatocyte receptors.

We have used photoreactive insulin analogues to investigate as related processes, early structural modification of the receptor-bound insulin molecule and internalisation of the insulin-receptor complex. In isolated rat hepatocytes an initial modification of bound insulin leads to the generation of a molecular species unchanged in molecular weight but with reduced receptor and antibody binding affinities and altered electrophoretic mobility. Using photoreactive insulin analogues and density gradient cell fractionation the insulin receptor complex has been shown to undergo internalisation from the plasma membrane to a low density vesicular fraction, the endosome. No labelled material was found in lysosomal fractions after up to 10 min incubation at 37 degrees C. The degree of labelling of the endosome fraction depended on the position of the photoreactive group within the insulin molecule. The data suggest that before or during endocytosis, a small peptide is proteolytically cleaved from the C terminus of the insulin B chain.

Demonstration that the insulin receptor undergoes an early structural modification following insulin binding.

Processing of the insulin receptor by hepatocytes was studied using a 125I-labelled photoreactive insulin derivative which could be covalently attached to the receptor and facilitate the analysis of receptor structure in isolated subcellular fractions by SDS-polyacrylamide gel electrophoresis. Following binding at the cell surface, the label was rapidly internalised and located in a low-density subcellular fraction ('endosomes'). The intact receptor (350 000 molecular weight) and binding (alpha) subunit (135 000), produced by in vitro disulphide reduction of the samples, were found in the plasma membrane fraction but not in endosomes. In endosomes, the label was concentrated in a band at 140 000 (non-reduced) which on reduction generated species of 100 000 and 68 000 predominantly. The insulin receptor therefore undergoes an early structural change during endocytosis. This modification does not involve complete disulphide reduction and may be due to a proteolytic event.

Protection against oxidative stress-induced insulin resistance in rat L6 muscle cells by mircomolar concentrations of alpha-lipoic acid.

In diabetic patients, alpha-lipoic acid (LA) improves skeletal muscle glucose transport, resulting in increased glucose disposal; however, the molecular mechanism of action of LA is presently unknown. We studied the effects of LA on basal and insulin-stimulated glucose transport in cultured rat L6 muscle cells that overexpress GLUT4. When 2-deoxy-D-glucose uptake was measured in these cells, they were more sensitive and responsive to insulin than wild-type L6 cells. LA, at concentrations < or = 1 mmol/l, had only small effects on glucose transport in cells not exposed to oxidative stress. When cells were exposed to glucose oxidase and glucose to generate H2O2 and cause oxidative stress, there was a marked decrease in insulin-stimulated glucose transport. Pretreatment with LA over the concentration range of 10-1,000 pmol/l protected the insulin effect from inhibition by H2O2. Both the R and S isomers of LA were equally effective. In addition, oxidative stress caused a significant decrease (approximately 50%) in reduced glutathione concentration, along with the rapid activation of the stress-sensitive p38 mitogen-activated protein kinase. Pretreatment with LA prevented both of these events, coincident with protecting insulin action. These studies indicate that in muscle, the major site of insulin-stimulated glucose disposal, one important effect of LA on the insulin-signaling cascade is to protect cells from oxidative stress-induced insulin resistance.

The effects of wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, on insulin-stimulated glucose transport, GLUT4 translocation, antilipolysis, and DNA synthesis.

PI 3-kinase, an enzyme that selectively phosphorylates the 3-position of the inositol ring, is acutely activated by insulin and other growth factors. The physiological significance of PI 3-kinase activation and, more specifically, its role in insulin action is an area under intense investigation. In this study, we have examined the role of PI 3-kinase activation in mediating selected metabolic and mitogenic effects of insulin employing the fungal metabolite wortmannin, a potent inhibitor of PI 3-kinase activity. In isolated rat and cultured 3T3-L1 adipocytes, wortmannin inhibited insulin-stimulated glucose transport (IC50 = 9 nM) without a significant effect on basal transport. Insulin-stimulated translocation of GLUT4 in isolated rat adipocytes was markedly inhibited by wortmannin. Wortmannin had no effect on either basal or insulin-stimulated glucose utilization in L6 myocytes, a skeletal muscle cell line in which GLUT1 is the predominant transporter isoform. Wortmannin also partially antagonized the antilipolytic effect of insulin on adenosine deaminase-stimulated lipolysis in isolated rat adipocytes. Furthermore, wortmannin caused a significant reduction in insulin-stimulated DNA synthesis in Fao rat hepatoma cells. We conclude that PI 3-kinase activation is necessary for maximum insulin-stimulated glucose transport, translocation of GLUT4, antilipolysis and DNA synthesis.

HLA-DR and DQ matching by DNA restriction fragment length polymorphism methods and the outcome of mixed lymphocyte reaction tests in unrelated bone marrow donor searches. The IMUST Study.

The use of DNA restriction fragment length polymorphism (DNA-RFLP) typing for HLA-DR and DQ genes was assessed in 96 patients who were HLA-A,B and DR matched by serology with one or more potential unrelated marrow donors (UD). Two hundred recipient-donor pairs from 10 transplant centres in the UK were studied. DNA-RFLP revealed serological errors in HLA-DR typing and identified additional recipient-donor mismatches. Of the 200 allegedly serologically matched pairs, 55 (28%) were mismatched for HLA-DR and/or DQ by DNA-RFLP typing. Of the 200 pairs, 68 (34%) mixed lymphocyte reactions (MLR) were negative and 132 (66%) positive. There was a significant correlation between DNA-RFLP defined mismatch and MLR positivity. However quantitative studies revealed no trend towards increasing MLR relative response index (RRI) with cumulative RFLP defined mismatch (i.e. for DR plus DQ compared with DR or DQ alone). RFLP matching for HLA-DR and DQ failed to predict a negative MLR. The RRI in the graft-versus-host direction was greater in RFLP matched pairs who carried HLA-DR4 than in matched pairs lacking DR4, suggesting that failure of RFLP to characterize DR4 subtypes was one reason why routine prediction of a negative MLR was not possible. Despite these limitations we have shown that DNA-RFLP is a reliable method for HLA-DR, DQ typing in routine UD searches in diverse clinical centres. By reducing the number of UD tested in MLR, RFLP typing can substantially reduce the work involved in donor selection.

Transgenic superoxide dismutase mice differ in opioid-induced analgesia.

Autoradiographic data from transgenic mice carrying the human Cu/Zn-superoxide dismutase gene demonstrate an increase in mu-opioid receptor concentration in dopaminergic-related areas and the central grey area. The relative potencies of mu-, delta- and kappa-opioid receptor agonists to induce antinociception in heterozygous and homozygous superoxide dismutase transgenic mice as well as four inbred strains were assessed to determine the functional significance of the increased receptor concentration. Increased superoxide dismutase activity results in an increased sensitivity to mu-agonists in a gene dosage-dependent manner. SOD/Tg/hom mice were less sensitive to the delta-agonist than were SOD/Tg/het mice. The superoxide dismutase transgene did not affect kappa-opioid receptor agonist sensitivity. These data suggest that delta-opioid receptors are not regulated in the same manner as mu-opioid receptors and that kappa-opioid receptors are unaffected by superoxide dismutase activity.

Alpha-lipoic acid: a multifunctional antioxidant that improves insulin sensitivity in patients with type 2 diabetes.

Alpha-Lipoic acid (LA) is a disulfide compound that is produced in small quantities in cells, and functions naturally as a co-enzyme in the pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase mitochondrial enzyme complexes. In pharmacological doses, LA is a multifunctional antioxidant. LA has been used in Germany for over 30 years for the treatment of diabetes-induced neuropathy. In patients with type 2 diabetes, recent studies have reported that intravenous (i.v.) infusion of LA increases insulin-mediated glucose disposal, whereas oral administration of LA has only marginal effects. If the limitations of oral therapy can be overcome, LA could emerge as a safe and effective adjunctive antidiabetic agent with insulin sensitizing activity.

Transgenic superoxide dismutase mice: Increased mesolimbic µ-opioid receptors results in greater opioid-induced stimulation and opioid-reinforced behavior.

Consequent to the insertion of the human Cu/Zn-superoxide dismutase (SOD) transgene, SOD transgenic mice (SOD-Tg) show higher concentrations of the primary receptor thought to be involved in opioid reinforcement (µ). These increases are observed in areas specifically associated with the primary neurotransmitter thought to be involved in addiction (dopamine), and in neuroanatomical regions thought to mediate substance abuse (mesolimbic). In the present study we have tested the idea that these increases in µ-receptors are associated with parallel changes in µ-mediated behaviors. Baseline and morphine-induced locomotor activity were significantly altered in the SOD-Tg mice. A qualitative change in the nature of acute and chronic morphine-induced locomotor activity was demonstrated by a significant change in the slope of the dose-effect curve. SOD-Tg mice were significantly more sensitive to the locomotor stimulant effects of morphine. Intravenous morphine-reinforced behavior was also altered in the SOD-Tg mice. SOD-Tg mice showed significant dose-related changes in operant lever-press responding maintained by morphine injection and significantly greater amounts of behavior were maintained by the drug than by vehicle under an intermittent schedule of reinforcement. In addition, SOD-Tg mice increased operant responding for the drug when the amount of behavior required to maintain drug intake increased 10-fold under a PR schedule of reinforcement. In contrast, in wild-type mice morphine injections failed to maintain greater amounts of behavior than vehicle, there were no dose-related changes in behavior, and when response requirements increased under the PR schedule, morphine intake decreased significantly. Thus, SOD transgene insertion significantly enhanced the efficacy of morphine as a reinforcer.

Hemorrhagic lymphadenopathy as a presenting feature of primary al amyloidosis.

Lymphadenopathy associated with hemorrhage as a presenting feature of primary (AL) amyloidosis has not previously been described. We report two such cases one of whom had an acquired factor X and IX deficiency. The clinical presentations were characterized by sudden spontaneous enlargement of lymph nodes followed by partial regression. In both cases significant delay in diagnosis, and hence treatment, occurred due to the mode of presentation. One patient died with rapidly progressive disease but the other has had an excellent response to therapy with high-dose melphalan (HDM, 200 mg/m2) and peripheral blood stem cell rescue. AL amyloid should be considered in all patients presenting with hemorrhagic lymphadenopathy.

Economic evaluation of oral sumatriptan compared with oral caffeine/ergotamine for migraine.

We conducted an economic comparison of oral sumatriptan with oral caffeine/ergotamine in the treatment of patients with migraine. Cost-effectiveness, cost-utility and cost-benefit analyses were conducted from societal and health-departmental perspectives. A decision tree was used. Utilities were assigned to health states using the Quality of Well-Being Scale. Simple and probabilistic sensitivity analyses were also carried out. From a societal perspective, using sumatriptan instead of caffeine/ergotamine resulted in an incremental cost-effectiveness ratio of -25 Canadian dollars ($Can) per attack aborted, an incremental cost-utility ratio of -$Can7507 per quality-adjusted life-year (QALY), and a net economic benefit of $Can42 per patient per year (1995 values). From the perspective of the health department, the incremental cost-effectiveness ratio was $Can98 per attack aborted, the incremental cost-utility ratio was $Can29,366 per QALY; the grade of recommendation based on past decisions regarding health technology for adoption into health insurance plans was 'moderate'. Sensitivity analysis showed that the results were robust to relatively large changes in the input variables. The incremental health benefits obtained from using oral sumatriptan rather than oral caffeine/ergotamine were achieved at moderately acceptable incremental costs, if past decisions on the adoption of other health technologies are used as a guide.

Secretion of radioactivity in breast milk following administration of 99Tcm-MAG3.

Measurements were made of the fraction of injected radioactivity which was secreted in breast milk following 99Tcm-MAG3 dynamic renal scans of two nursing mothers. The activity concentration in the milk expressed at different times after injection was found to decrease monoexponentially, with effective half-lives of 3.2 and 4.0 h. Two models were applied to each set of data and predicted an overall mean infant effective dose equivalent per unit administered activity of 2.9 muSv MBq-1 and maximum of 4.5 muSv MBq-1. The results demonstrated that it was not essential to interrupt breast feeding following administration of 100 MBq 99Tcm-MAG3 for a dynamic renal scan. If a renal perfusion scan is performed using greater activities of 99Tcm-MAG3, the mother should interrupt feeding and not resume until measurements on her expressed milk samples indicate that the effective dose equivalent to the infant will be less than 1 mSv. However, it was noted that a considerably lower radiation dose to the infant could be achieved by using 99Tcm-DTPA. Therefore, it was concluded that whenever clinically appropriate 99Tcm-DTPA should be used for both types of renal investigations of breast-feeding mothers.

Early language and communicative abilities of children with periventricular leukomalacia.

Ten 2-year-old children with periventricular leukomalacia (PVL), a brain injury associated with prematurity, were evaluated using language samples. Five children scored less than 80 on cognitive testing (delayed). Five children with this disorder and normal cognitive scores were assessed at two ages, matched with the delayed group on CA and developmental level. The delayed group produced significantly fewer lexical tokens and spontaneous verbal utterances than did the CA-matched group. No significant differences were observed between the delayed group and either comparison group on other measures of lexicon, grammar, or communication. The data demonstrate a relation between cognitive abilities and measures of verbal productivity in children with PVL.

Effects of diet acidity and protein level or source of calcium on the performance, gastrointestinal content measurements, bone measurements, and carcass composition of gilt and barrow weanling pigs.

A total of 228 crossbred weanling pigs (average age of 25 d and BW of 6.44 kg) were used in two trials to evaluate the responses to sex, diet acidity, protein level, and source of calcium on the performance, gastrointestinal digesta measurements, bone measurements, and carcass composition. Diet acidity was manipulated by varying the sources of supplemental phosphorus in the diets. Trial 1 (5 wk) was conducted as a 2 x 3 x 2 factorial to evaluate sex (gilts and barrows), diet acidity (pH 5.9 and .90% P, pH 6.1 and .63% P, and pH 6.9 and .63% P), and level of protein (16 and 22% CP). In Trial 2 (6 wk), diet acidity (pH 5.5, 5.9, and 6.8, all with .7% P) and Ca sources (CaCO3 and CaSO4) were used with gilts and barrows. The sex x diet acidity interactions were significant for ADG in both trials. Barrows seemed to respond to both the more acidic diets and the buffered phosphate diets even though the pH was less acidic than that of the unbuffered diets. Gilts responded only to the more acidic diets. In Trial 1, gilts ate more and grew faster (P < .05) than barrows, but no sex effects on performance were observed in Trial 2. Pigs fed 22% CP diets grew faster (P < .001) and more efficiently (P < .001) than did pigs fed 16% CP diets, but protein level x diet acidity and protein level x sex interactions were not significant. Stomach digesta DM, pH, and titration value were not consistently influenced by sex and diet acidity in Trials 1 and 2, by protein level in Trial 1, and by calcium source in Trial 2. Only the sex x diet acidity interaction for stomach DM tended to be significant in both trials; gilts fed the less acidic diets had the lowest DM, whereas barrows fed the more acidic diets had the lowest DM values. Although not significant in every case in both trials, bone (average of metacarpal and metatarsal) volume was lower and specific gravity and shear stress values were higher for gilts than for barrows. Pigs fed 16% CP diets had higher specific gravity (P < .05) and stress (P < .06) values than pigs fed 22% CP diets. A protein level x diet acidity interaction (P < .03) for stress suggested that pigs fed 22% CP diets were unaffected by diet acidity, whereas pigs fed 16% CP had the highest stress values when fed the more acidic diet and the lower P level.(ABSTRACT TRUNCATED AT 250 WORDS)

Additive genetic relationships between heifer pregnancy and scrotal circumference in Hereford cattle.

The objective of this study was to determine an appropriate method for using yearling scrotal circumference observations and heifer pregnancy observations to produce EPD for heifer pregnancy. We determined the additive genetic effects of and relationship between scrotal circumference and heifer pregnancy for a herd of Hereford cattle in Solano, New Mexico. The binary trait of heifer pregnancy was defined as the probability of a heifer conceiving and remaining pregnant to 120 d, given that she was exposed at breeding. Estimates of heritability for heifer pregnancy and scrotal circumference were .138+/-.08 and .714+/-.132, respectively. Estimates of fixed effects for age of dam and age were significant for heifer pregnancy and bull scrotal circumference. The estimate of the additive genetic correlation between yearling heifer pregnancy and yearling bull scrotal circumference was .002+/-.45. Additional analyses included models with additive genetic groups for scrotal circumference EPD for heifer pregnancy or heifer pregnancy EPD for scrotal circumference to account for a potential nonlinear relationship between scrotal circumference and heifer pregnancy. Results support the development of a heifer pregnancy EPD because of a higher estimated heritability than previously reported. The development of a heifer pregnancy EPD would be an additional method for improving genetic merit for heifer fertility.

Effects of dietary pH and phosphorus source on performance, gastrointestinal tract digesta, and bone measurements of weanling pigs.

Crossbred pigs (n = 144, average age and weight = 28 +/- 3 d, 7.5 kg) were used in two 6-wk trials to assess the effects of dietary pH and P source on growth performance, gastrointestinal digesta pH and chloride ion concentration (Cl-), and bone characteristics. Treatments were randomly allotted within blocks (based on weight within gender) to a 3 x 2 factorial arrangement with three dietary pH levels (5.4, 6.0, and 6.7) and two P sources: dicalcium phosphate (DCP) and defluorinated phosphate (DFP). Pigs fed the pH 6.7 diet had reduced ADG (P less than .01) and average daily feed intakes (ADFI; P less than .001) during wk 1 to 3 and overall compared with pigs fed the pH 6.0 diet, but ADG and ADFI were not affected when the pH 5.4 diet was fed. There was a dietary pH x P source interaction (P less than .05) for ADFI. Pigs had decreased ADFI as dietary pH was increased from 6.0 to 6.7 for both DCP and DFP, but ADFI was similar for the pH 6.0 and 5.4 diets with DFP, whereas ADFI was greater for the pH 5.4 diet with DCP. Dietary pH did not influence ADFI:ADG ratio (F:G; P greater than .05), and P source had no effect (P greater than .05) on either ADG, ADFI, or F:G.(ABSTRACT TRUNCATED AT 250 WORDS)