bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypothalamic Gonadotrophin‐Releasing Hormone Expression in Female Monkeys with Different Sensitivity to Stress
Authors: Centeno M.‐L. , Sanchez R. L. , Cameron J. L. , Bethea C. L.
Published: June 2007

Psychosocial stress, combined with mild dieting and moderate exercise, are observed in women seeking treatment for hypothalamic amenorrhea. Using female cynomolgus macaques, we previously reported that the same combination of mild stresses suppressed reproductive hormone secretion and menstrual cycles in some individuals (stress‐sensitive, SS), but not in others (highly stress‐resilient, HSR). Compared to HSR monkeys, SS monkeys exhibited lower oestradiol and progesterone levels at the midcycle peak and decreased gene expression in the central serotonergic system during nonstressed cycles. Because steroids and serotonin impinge upon the hypothalamic‐pituitary‐gonadal (HPG) axis, we hypothesised that the differences between SS and HSR monkeys in the sensitivity of the HPG axis to stress may ultimately manifest in differences in the gonadotrophin‐releasing hormone (GnRH) system. GnRHin situhybridisation and immunohistochemistry were performed with hypothalamic sections from SS and HSR animals, euthanised in the early follicular phase of a nonstressed menstrual cycle. Compared to HSR monkeys, SS monkeys exhibited a significantly higher number and density of GnRH cell bodies, as well as a higher number of soma with extremely robust expression of GnRH mRNA, but SS monkeys exhibited a lower density of immunostained GnRH fibres in the median eminence. We suggest that neuronal mechanisms involved in the control of GnRH synthesis, transport and release differ in SS compared to HSR animals.
Biologic activity of dirlotapide, a novel microsomal triglyceride transfer protein inhibitor, for weight loss in obese dogs
Authors: WREN J. A. , KING V. L. , CAMPBELL S. L. , HICKMAN M. A.
Published: June 2007

Dirlotapide is a novel microsomal triglyceride transfer protein inhibitor intended for the treatment and management of obesity in dogs. The biologic effects of dirlotapide, weight loss, decreased food intake, increased fecal fat, decreased serum cholesterol, and body composition, were evaluated in a controlled, blinded study. Sixteen obese beagles were randomized to treatment with placebo (n = 4) or dirlotapide (n = 12) following a 2‐week acclimation period in which baseline data were collected. The dirlotapide dose, adjusted to produce weight loss for 3 months and then stabilize body weight for 1 month (weight management), produced a significant difference (expressed as a percentage of baselines) in weekly weight loss, food intake, fecal fat, serum cholesterol concentration, and body composition (measured by dual energy X‐ray absorptiometry) compared with placebo treatment (P < 0.05). The initial dirlotapide dosage of 0.5 mg/kg (10 times the initial label dose) resulted in a high rate of weight loss (3.3% weekly) and anorexia, emesis, and loose stools for some dogs. A 25% dose reduction (mean dosage: 0.36 mg/kg) followed by biweekly 25% dose adjustments based on individual weight loss, produced 1–2% weekly weight loss and total weight loss of 18.8% in 12 weeks at a final mean dosage of 0.41 mg/kg (range: 0.15–0.60); a dosage range of 0.10–0.34 mg/kg stabilized body weight. Body weight changes for placebo‐treated dogs were −0.8% to +0.9% weekly; total weight gain during the weight loss phase was 10.6%. No apparent change in food intake, percentage of fecal fat, and serum cholesterol was observed in the placebo group. Food intake and body weight increased when dirlotapide was discontinued. Dirlotapide produced weight loss by both reducing appetite (about 90% of the weight loss activity) and by increasing fecal fat excretion (about 10% of the weight loss activity).
The safety of dirlotapide in dogs
Authors: WREN J. A. , KING V. L. , KRAUTMANN M. J. , GOSSELLIN J. , KERLIN R. L. , HICKMAN M. A. , SCHMAHAI T. J.
Published: June 2007

The safety of dirlotapide in dogs was evaluated in two studies with parallel designs. In an acute tolerance study, 24 beagles (six dogs per treatment) were treated orally once daily for 14 days with placebo or dirlotapide at 2.5, 5.0, or 10.0 mg/kg/day. In a margin‐of‐safety study, 38 overweight, neutered beagles were treated orally once daily for 3 months with dirlotapide at doses up to 0.5 mg/kg/day (six dogs), 1.5 mg/kg/day (12 dogs) and 2.5 mg/kg/day (six dogs). Control dogs received placebo at 0.3 mL/kg/day (10 dogs) and 0.5 mL/kg/day (four dogs). Results were similar for both studies, and no serious adverse events were observed. Dirlotapide was clinically well‐tolerated in dogs at dosages up to 10 mg/kg/day for 14 days and 2.5 mg/kg/day for 3 months. Dirlotapide produced the expected decrease in food intake and body weight (up to 20–40%) without ill effects. Clinical, pathologic, and histopathologic findings were reversible and consistent with suppression of food intake and rapid weight loss produced by elevated dirlotapide dosages. In both studies, sporadic emesis and loose stools were observed in both placebo and dirlotapide‐treated dogs. Incidence of emesis generally increased with dose and decreased with treatment time. Elevations in hepatic transaminase activity were seen in dogs treated with more than 1.5 mg/kg dirlotapide daily, but were not associated with clinical signs or microscopic evidence of hepatic degeneration or necrosis.
An evaluation of dirlotapide to reduce body weight of client‐owned dogs in two placebo‐controlled clinical studies in Europe
Authors: GOSSELLIN J. , MCKELVIE J. , SHERINGTON J. , WREN J. A. , EAGLESON J. S. , ROWAN T. G. , SUNDERLAND S. J.
Published: June 2007

The clinical efficacy for weight loss and safety of dirlotapide in dogs were evaluated in two multi‐centre studies with parallel designs. Overweight, adult dogs (n = 245) of various breeds were randomized to treatment with dirlotapide or placebo in a 2:1 ratio. Dirlotapide was administered orally once daily to dogs at an initial dose of 0.05 mg/kg/day commencing on day 0 and doubled after 14 days. Every 28 days, dogs were examined, weighed, body condition scores (BCS) were recorded, and dose was adjusted to meet weight loss targets. Each study comprised three consecutive phases: weight‐loss (up to day 196); weight‐stabilization (84 days); and post‐treatment (28 days). pre‐treatment feeding and exercise regimens were continued during treatment. Dirlotapide‐treated dogs showed mean weight loss of 15.9% (study A) and 14.0% (study B) by the end of weight loss phase (up to day 196). Percentage weekly weight losses for dirlotapide were significantly greater than for placebo (P ≤ 0.0002). Emesis and diarrhoea were experienced in both treatments but were more frequent with dirlotapide; resolution was spontaneous. BCS improved for 75.7–82.5% of dogs on dirlotapide treatment compared with 15.4–41.4% for placebo. Mean dirlotapide dosage at end of weight‐loss phase was 0.38 (study A) and 0.29 (study B) mg/kg initial body weight/day. Dirlotapide was found to be clinically safe and effective in the reduction of body weight in overweight dogs.
Efficacy and safety of dirlotapide in the management of obese dogs evaluated in two placebo‐controlled, masked clinical studies in North America
Authors: WREN J. A. , RAMUDO A. A. , CAMPBELL S. L. , KING V. L. , EAGLESON J. S. , GOSSELLIN J. , SUNDERLAND S. J.
Published: June 2007

Dirlotapide was evaluated in the management of obesity in dogs in two multicenter, clinical studies in North America. A total of 335 obese dogs of various breeds were randomized to dirlotapide or placebo in a 2:1 ratio. Dirlotapide was administered orally once daily to dogs at an initial dose of 0.05 mg/kg, increased after 14 days to 0.1 (study B, label dose) or 0.2 mg/kg (study A) and then adjusted according to individual weight loss at 28‐day intervals. Dogs were examined and weighed, and body condition scores (BCSs) were recorded every 28 days. Study A had three consecutive phases: weight loss (16 weeks, day 0–112); weight management (12 weeks); and post‐treatment (8 weeks). Study B had a weight loss phase only. For dirlotapide‐treated dogs, mean weight loss by day 112 was 11.8–14.0% compared with 3.0–3.9% for placebo (P = 0.0001). In study A, weight losses for dirlotapide were 19.3% after 12 weeks of weight management and 16.7% (regain of 3.4%) by 8 weeks after dirlotapide was discontinued. In both studies, dogs in both treatments had emesis, lethargy, anorexia, diarrhea, and mildly elevated hepatic transaminase activity, that resolved spontaneously with time. These were experienced more frequently with dirlotapide. Improved activity levels and BCS for >50% dogs were reported with dirlotapide. Dirlotapide was safe and effective in the reduction and management of body weight in obese dogs.
Lower reproductive success in hybrid fur seal males indicates fitness costs to hybridization
Authors: LANCASTER MELANIE L. , BRADSHAW COREY J. A. , GOLDSWORTHY SIMON D. , SUNNUCKS PAUL
Published: June 2007

Hybridization among organisms can potentially contribute to the processes of evolution, but this depends on the fitness of hybrids relative to parental species. A small, recently formed population of fur seals on subantarctic Macquarie Island contains a high proportion of hybrids (17–30%) derived from combinations of three parental species: Antarctic, subantarctic and New Zealand fur seals. Mitochondrial control‐region data (restriction fragment length polymorphisms) and nine microsatellites were used to determine the species composition of breeding adults, and hybrid male fitness was measured by comparing reproductive success (number of genetically inferred paternities) of hybrid and pure‐species territory males over 6 years. No correlations were found between male reproductive success and three genetic measures of outbreeding, but this may be due to a relatively small number of dominant males analysed. Territory males fathered 63% of pups, but hybrid males had lower reproductive success than pure‐species males despite having the same ability to hold territories. A greater proportion of females in hybrid male territories conceived extra‐territorially than those in territories of pure‐species males, and most (70 of 82) mated with conspecifics. This suggests the presence of reproductive isolating mechanisms that promote positive assortative mating and reduce the production of hybrid offspring. Although we found no evidence for male sterility in the population, mechanisms that reduce lifetime reproductive success may act to decrease the frequency of hybrids. Our study has identified a disadvantage of hybridization — reduced reproductive success of hybrid sons — that may be contributing to the persistence of pure lineages at Macquarie Island and the temporal decline in hybridization observed there.
Landscape‐level gene flow inLobaria pulmonaria, an epiphytic lichen
Authors: WERTH SILKE , GUGERLI FELIX , HOLDEREGGER ROLF , WAGNER HELENE H. , CSENCSICS DANIELA , SCHEIDEGGER CHRISTOPH
Published: June 2007

Epiphytes are strongly affected by the population dynamics of their host trees. Owing to the spatio‐temporal dynamics of host tree populations, substantial dispersal rates — corresponding to high levels of gene flow — are needed for populations to persist in a landscape. However, several epiphytic lichens have been suggested to be dispersal‐limited, which leads to the expectation of low gene flow at the landscape scale. Here, we study landscape‐level genetic structure and gene flow of a putatively dispersal‐limited epiphytic lichen,Lobaria pulmonaria. The genetic structure ofL. pulmonariawas quantified at three hierarchical levels, based on 923 thalli collected from 41 plots situated within a pasture–woodland landscape and genotyped at six fungal microsatellite loci. We found significant isolation by distance, and significant genetic differentiation both among sampling plots and among trees. Landscape configuration, i.e. the effect of a large open area separating two forested regions, did not leave a traceable pattern in genetic structure, as assessed with partial Mantel tests and analysis of molecular variance. Gene pools were spatially intermingled in the pasture–woodland landscape, as determined by Bayesian analysis of population structure. Evidence for local gene flow was found in a disturbed area that was mainly colonized from nearby sources. Our analyses indicated high rates of gene flow ofL. pulmonariaamong forest patches, which may reflect the historical connectedness of the landscape through gene movement. These results support the conclusion that dispersal inL. pulmonariais rather effective, but not spatially unrestricted.
Fc gamma Receptor IIa (CD32) Polymorphism and Antibody responses to Asexual Blood‐stage Antigens of Plasmodium falciparum Malaria in Sudanese Patients
Authors: Nasr A. , Iriemenam N. C. , Troye‐Blomberg M. , Giha H. A. , Balogun H. A. , Osman O. F. , Montgomery S. M. , ElGhazali G. , Berzins K.
Published: June 2007

In a prospective clinical study in New Halfa Teaching Hospital, the possible association between FcγRIIa‐R/H131 polymorphism and anti‐malarial antibody responses with clinical outcome of Plasmodium falciparum malaria among Sudanese patients was investigated. A total of 256 individuals were consecutively enrolled, comprising 115 patients with severe malaria, 85 with mild malaria and 56 malaria‐free controls. Genotyping of FcγRIIa‐R/H131 dimorphism was performed using gene‐specific polymerase chain reaction (PCR) amplification with allele‐specific restriction enzyme digestion of the PCR product. The antibody responses to asexual blood‐stage antigens were assessed by an enzyme‐linked immunosorbent assay. The frequency of the FcγRIIa‐R/R131 genotype was significantly higher in those with severe malaria when compared with patients with mild malaria, while the FcγRIIa‐H/H131 genotype showed a significant association with mild malaria. A reduced risk of severe malaria with IgG3 antibodies in combination with the H/H131 genotype was observed. Furthermore, low levels of IgG2 antibodies reactive with the Pf332‐C231 antigen were also associated with lower risk of severe malaria in individuals carrying the H131 allele. The levels of IgG1 and IgG3 antibodies were statistically significantly higher in the mild malaria patients when compared with the severe malaria patients. Taken together, our study revealed that the FcγRIIa‐R/R131 genotype is associated with the development of severe malaria, while the H/H131 genotype is more likely to be associated with mild malaria. Our results also revealed that the natural acquisition of immunity against clinical malaria appeared to be more associated with IgG1 and IgG3 antibodies, signifying their roles in parasite‐neutralizing immune mechanisms.
De‐aluminated Zeolite Y as a Tool to Study Endocytosis, A Delivery System Revealing Differences between Human Peripheral Dendritic Cells
Authors: Andersson L. I. M. , Eriksson H.
Published: June 2007

We report the use of nanometre‐sized zeolite particles as a novel approach to follow the endosomal acidification and proteolysis inside a viable cell. The method was verified by using human peripheral monocytes, a well known endocytosing cell population. Zeolite particles were subsequently used to investigate the endocytosing mechanisms of human peripheral dendritic cells (DC). Probes detecting pH neutral and acidic endosomes were adsorbed to de‐aluminated zeolite Y, and used to detect endocytosis in immature human peripheral blood DC. Both the myeloid (mDC) and the plasmacytoid (pDC) dendritic cell subsets had an endocytosing capacity comparable with peripheral blood monocytes. However, the majority of both subsets of DC retained their endosomes at a neutral pH during the first hours after endocytosis and only a small number of the mDC showed any formation of acidic endosomes. Proteolytic degradation of endocytosed proteins was detected using self‐quenched DQ‐ovalbumin adsorbed to zeolite particles. Interestingly, a clear difference in proteolytic degradation of endocytosed ovalbumin was observed between the two subsets of DC. The mDC showed an efficient degradation of ovalbumin, while the pDC population displayed no or only minor proteolytic degradation. In conclusion, zeolite particles provide a useful tool to study the endocytosing mechanisms, and an efficient carrier of bio‐molecules into the endosomal pathways of viable cells.
COMT genotype increases risk for bipolar I disorder and influences neurocognitive performance
Authors: Burdick Katherine E , Funke Birgit , Goldberg Joseph F , Bates John A , Jaeger Judith , Kucherlapati Raju , Malhotra Anil K
Published: June 2007

Objectives:  Bipolar disorder (BPD) is an affective disorder characterized by episodes of depression and mania. Cognitive impairment in patients with BPD is common and recent data suggest that it may represent a trait‐like feature of the illness, as it persists during periods of wellness and co‐segregates in families of bipolar patients. This suggests an underlying genetic predisposition towards cognitive impairment in patients with BPD; however, there have been few studies investigating the effects of candidate genes on this symptom domain. The catechol‐O‐methyl transferase (COMT) gene is located on chromosome 22q11 and is involved in the metabolism of dopamine and norepinephrine. A large body of evidence suggests that COMT is associated with cognitive performance in patients with schizophrenia and in healthy volunteers but there have been no reports of its relationship to cognition in BPD.

Methods:  We genotyped 52 Caucasian bipolar I probands and 102 Caucasian healthy controls across four single nucleotide polymorphisms (SNPs) within the COMT gene and administered a cognitive screening battery. We first assessed the relationship between COMT genotype and diagnosis and then tested for effects on cognition.

Results:  We observed a modest but significant association between SNP rs165599 and BPD I, with the g allele being over‐represented in cases versus controls (odds ratio, OR = 2.41; allelic p = 0.02; genotypic p = 0.04). Further, we found a relationship between the risk allele at this SNP and poorer performance on measures of verbal memory [California Verbal Learning Test (CVLT) Trials 1–5; p = 0.005, η2 = 0.07] particularly with regard to prefrontal aspects of learning (CVLT semantic cluster; p = 0.037, η2 = 0.04) in patients with BPD and in healthy controls. The common Val158Met polymorphism was not associated with diagnosis (p = 0.32) or cognition in our sample.

Conclusions:  These data suggest that COMT genetic variation at SNP rs165599 is associated with BPD I and influences prefrontal aspects of verbal memory in bipolar patients and healthy controls.
Early identification and high‐risk strategies for bipolar disorder
Authors: Correll Christoph U , Penzner Julie B , Lencz Todd , Auther Andrea , Smith Christopher W , Malhotra Anil K , Kane John M , Cornblatt Barbara A
Published: June 2007

Objectives:  To describe and compare the relative merits of different identification strategies for individuals at risk for bipolar disorder (BPD).

Methods:  Selective review of data that support early identification in BPD, with a particular focus on emerging clinical high‐risk strategies.

Results:  Early detection of individuals at risk for BPD can utilize genetic, endophenotypic and clinical methods. Most published work focuses on genetic familial endophenotypic risk markers for BPD. However, despite encouraging results, problems with specificity and sensitivity limit the application of these data to early prevention programs. In addition, offspring studies of BPD patients systematically exclude the majority of subjects without a first‐degree bipolar relative. On the other hand, emerging work in the clinical‐high‐risk arena has already produced encouraging results. Although still preliminary, the identification of individuals in subsyndromal or attenuated symptom ‘prodromal’ stages of BPD seems to be an under‐researched area that holds considerable promise deserving increased attention. Required next steps include the development of rating tools for attenuated and subsyndromal manic and depressive symptoms and of prodromal criteria that will allow prodromal symptomatology to be systematically studied in patients with recent‐onset bipolar, as well as in prospective population‐based phenomenology trials and attenuated symptom‐based high‐risk studies.

Conclusions:  Given the current limitations of each early identification method, combining clinical, endophenotypic and genetic strategies will increase prediction accuracy. Since reliable biological markers for BPD have not been established and since most patients with BPD lack a first‐degree relative with this disorder, clinical high‐risk approaches have great potential to inform early identification and intervention programs.
Use of the DiaMed Impact R to test platelet function in stored platelet concentrates
Authors: Morrison A. , Hornsey V. S. , Prowse C. V. , MacGregor I. R.
Published: June 2007

Background and Objectives The DiaMed Impact R tests platelet function under close to physiological flow conditions using cone and plate technology. An image analyser quantifies the adhered platelets and results are expressed as percentage of well surface covered by aggregates (SC %) as an index of adhesion and average size of the aggregates (AS µm2) as an index of aggregation. The machine is designed to use whole blood and the aim of this study was to determine if it could be used to assess platelet function in platelet concentrates (PC).

Material and Methods  Platelet concentrates were mixed with various ratios of platelet‐poor plasma (PPP) or ABO‐compatible routine leucoreduced red cells in saline–adenine–glucose–mannitol. The effects of platelet counts, haematocrit, shear rate and time of activation upon SC and AS were evaluated to identify optimized assay conditions. Routine PCs were then tested on Days 2, 5 and 7. Samples were also stored at 4 or 37 °C for 1 to 2 h before assay to see if function was altered.

Results  Platelet concentrate in PPP resulted in no detectable platelet adhesion. However, addition of red cells to PC resulted in measurable platelet adhesion and aggregation. Optimal conditions were identified as shear rate of 1800 per second, 4‐min activation, platelet count between 250 and 400 × 106 per ml, haematocrit between 30 and 40%. When stored PCs were tested under these conditions we observed median values of 8·2% for SC and 32·7 µm2 for AS at 2 days, which reduced to 6.9% and 25·0 µm2, respectively, after 5‐day storage and 6·8% and 21·0 µm2 after 7 days.

Conclusion  We were able to reconstitute PCs by adding red cells and identified conditions to allow platelet adhesion and aggregation functions of PCs to be measurable in the DiaMed Impact R. Platelet functions of adhesion and aggregation were shown to decrease during storage but improved after a 1‐h treatment at 37 °C.
Cryosupernatant and solvent detergent fresh‐frozen plasma (Octaplas) usage at a single centre in acute thrombotic thrombocytopenic purpura
Authors: Scully M. , Longair I. , Flynn M. , Berryman J. , Machin S. J.
Published: June 2007

Background  Thrombotic thrombocytopenic purpura (TTP) is an acute, life‐threatening disorder and plasma exchange (PEX) remains the mainstay of treatment.

Methods  We reviewed 50 acute TTP episodes to establish the efficacy and safety of cryosupernatant (CPP) and Octaplas.

Results  Twelve episodes used CPP only and 15 episodes started with CPP and changed to Octaplas. Once Octaplas had been used, it was continued on further admissions. Cryosupernatant was used exclusively in 24% and Octaplas exclusively in 42% of all episodes. The number of citrate reactions and allergic (plasma) reactions were halved in those receiving only Octaplas compared with cryosupernatant. There were 22 line infections and in approximately 70% of cases the infection was associated with a reduction in platelet count. In all 50 episodes, the only documented thrombosis was a superficial non‐central vein. In episodes receiving only cryosupernatant or Octaplas, there was no significant difference in the median number of PEX to remission, 7·0 (interquartile range, IQR 5–8·8) and 8·0 (IQR 6·5–22), respectively. Baseline viral screen in all episodes was negative after discharge following an acute episode.

Conclusion  There was no difference in number of PEX to remission with cryosupernatant and solvent/detergent fresh‐frozen plasma (Octaplas). However, allergic/urticarial and citrate reactions were more common with cryosupernatant. There was no documented viral transmission with either product.
Influence of pea lectin expressed transgenically in oilseed rape (Brassica napus) on adult pollen beetle (Meligethes aeneus)
Authors: Lehrman A. , Åhman I. , Ekbom B.
Published: June 2007

Adult pollen beetles were exposed to three transgenic lines of Brassica napus L. expressing pea lectin up to 0.7% of total soluble protein in anthers. Two lines not expressing the pea lectin were used as controls. Adult responses were recorded in two experiments where beetles were fed either racemes or anthers. There was no effect of plant line on feeding rate, weight change or oviposition rate. A slightly reduced egg size was recorded when beetles were feeding on one of the plant lines with high concentration of pea lectin. Previous studies on the effect of pea lectin on pollen beetles have only focused on larval performance. The results of this study suggest that pea lectin has no adverse effect on the pest in its most damaging life stage.
Olfactory response of a predatory mirid to herbivore induced plant volatiles: multiple herbivory vs. single herbivory
Authors: Moayeri H. R. S. , Ashouri A. , Poll L. , Enkegaard A.
Published: June 2007

Plants infested with a single herbivore species can attract natural enemies through the emission of herbivore‐induced plant volatiles (HIPVs). However, under natural conditions plants are often attacked by more than one herbivore species. We investigated the olfactory response of a generalist predators Macrolophus caliginosus to pepper infested with two‐spotted spider mites, Tetranychus urticae, or green peach aphid, Myzus persicae, vs. plants infested with both herbivore species in a Y‐tube olfactometer set up. In addition, the constituents of volatile blends from plants exposed to multiple or single herbivory were identified by gas chromatography‐mass spectrometry (GC‐MS). The mirid bugs showed a stronger response to volatiles emitted from plants simultaneously infested with spider mites and aphids than to those emitted from plants infested by just one herbivore, irrespective of the species. Combined with results from previous studies under similar conditions we infer that this was a reaction to herbivore induced plant volatiles. The GC‐MS analysis showed that single herbivory induced the release of 22 additional compounds as compared with the volatiles emitted from clean plants. Quantitative analyses revealed that the amount of volatile blends emitted from pepper infested by both herbivores was significantly higher than that from pepper infested by a single herbivore. Moreover, two unique substances were tentatively identified (with a probability of 94% and 91%, respectively) in volatiles emitted by multiple herbivory damaged plants: α‐zingiberene and dodecyl acetate.
How compliant are we with guidelines for coronary angiography in clinical practice?
Authors: Leung D. Y. , Hallani H. , Lo S. T. , Hopkins A. P. , Juergens C. P.
Published: June 2007

Background: The American College of Cardiology and American Heart Association have published guidelines for coronary angiography. We evaluated the compliance rate with these guidelines in clinical practice, its correlation to results of angiography and aimed to identify problem areas of non‐compliance.

Methods: We prospectively evaluated 802 consecutive referrals for coronary angiography over 5 months in 2002 in a tertiary referral hospital. These referrals were assessed by two independent reviewers blinded to the results of angiography.

Results: Patient age was 62 ± 11 years (522 men, 433 inpatients, 369 day‐only patients). Referrals were outside published guidelines in 34.3 and 36.2% as evaluated by the two reviewers (concordance rate 88.2%, κ = 0.74, p < 0.001). Intraobserver agreement was 97.5%. The rate of angiography showing either normal arteries or only minor diseases (<50%) was higher for referrals outside guidelines (68.4 vs 22.6%, P < 0.001). Compliance rate was high with indications of non‐ST‐elevation myocardial infarction (99.2%) and ST‐elevation myocardial infarction (95.8%), valvular disease (80%) and arrhythmia (80%). Compliance rate was lower with assessment of dyspnoea or heart failure (74.3%) and before non‐cardiac surgery (72.7%) and was particularly low with assessment of chest pain (53.2%). Younger age (odds ratio (OR) 1.04, P < 0.001), female sex (OR 2.67, P < 0.001), day‐only procedure (OR 2.27, P < 0.001) and non‐invasive cardiologist referrer (OR 1.41, P = 0.046) were independent predictors of non‐compliance.

Conclusion: Referrals for coronary angiography were outside guidelines in a significant proportion of patients. Rate of negative angiography was higher when the referrals were outside guidelines. Problematic areas of non‐compliance could be identified. Measures specifically targeting these areas may be more effective in improving the overall guideline compliance in clinical practice.
Drug utilization evaluation of i.v. paracetamol at a large teaching hospital
Authors: Ghiculescu R. A. , Kubler P. A. , Gleeson P.
Published: June 2007

Background: I. v. paracetamol has recently become available in Australia for the treatment of pain when the oral or rectal administration route is not accessible. Our primary aim was to assess compliance with prescribing guidelines and our secondary aim to evaluate the safety of i.v. paracetamol use (4 g/day) and the effect of patient comorbidities on drug safety.

Methods: Eighty‐five consecutive patients were identified through the pharmacy dispensing system at a 900‐bed, metropolitan, primary care and tertiary referral hospital over a period of 7 months from December 2005 to June 2006. Cross‐sectional evaluation by patient interview, review of medical records and pathology parameters were carried out. The study has been approved by the Royal Brisbane and Women’s Hospital Human Research Ethics Committee.

Results: I.v. paracetamol was given for pain following abdominal surgery (90%) and musculoskeletal pain (10%). The comorbid conditions included severe renal impairment (9.4%), alcohol dependence (3.5%), pre‐existing liver failure (2.4%) and malnutrition (18.8%).

Prescribing guidelines were not adhered to in 25% of patients. The main cause for discordance observed in 90% of this group was the administration of i.v. paracetamol despite the presence of an alternative route of administration. Eight patients received i.v. paracetamol despite not having had a surgical procedure. Twelve patients received i.v. paracetamol for longer than 48 h; no injection site reactions or toxicity were noted.

Conclusion: A lack of concordance between i.v. paracetamol use and prescribing guidelines was identified. There were no new safety concerns.
Sleep health New South Wales: chronic sleep restriction and daytime sleepiness
Authors: Bartlett D. J. , Marshall N. S. , Williams A. , Grunstein R. R.
Published: June 2007

Aims:The aim of this study was to provide the first population‐based descriptions of typical sleep duration and the prevalence of chronic sleep restriction and chronic sleepiness in community‐dwelling Australian adults.

Methods:Ten thousand subjects randomly selected from the New South Wales electoral roll, half aged 18–24 years and the other half aged 25–64 years were posted a questionnaire asking about sleep behaviour, sleepiness and sleep disorders.

Results:Responses were received from 3300 subjects (35.6% response rate). The mean ± standard deviation of sleep duration was 7.25 ± 1.48 h/night during the week and 7.53 ± 2.01 h/night in the weekends. Of the working age group, 18.4% reported sleeping less than 6.5 h/night. Chronic daytime sleepiness was present in 11.7%. Logistic modelling indicated that the independent risk factors for excessive daytime sleepiness were being older, sleeping less than 6.5 h per night during the week, getting qualitatively insufficient sleep, having at least one symptom of insomnia and lacking enthusiasm (marker of depression).

Conclusion:In New South Wales almost one‐fifth of the people are chronically sleep restricted and 11.7% are chronically sleepy. Chronic sleepiness was most commonly associated with voluntarily short sleep durations and symptoms of insomnia and depression. If the experimentally observed health effects of sleep restriction also operate at a population level, this prevalence of chronic sleep restriction is likely to have a significant influence on public health in Australia.
Has the use of disease‐modifying anti‐rheumatic drugs changed as a consequence of controlled access to high‐cost biological agents through the Pharmaceutical Benefits Scheme?
Authors: Lu C. Y. , Williams K. M. , Day R. O.
Published: June 2007

Background: A prerequisite for access to biological agents for the treatment of rheumatoid arthritis under Australia’s Pharmaceutical Benefits Scheme (PBS) is evidence of an adequate trial of conventional disease‐modifying anti‐rheumatic drugs (DMARDs). The aim of this study was to examine whether there were changes in prescribing DMARDs since the introduction of the PBS criteria for access to biologicals in August 2003.

Methods: A retrospective study was undertaken of the national use of DMARDs in the period before and after the introduction of biologicals under the PBS. Dispensing data were analysed for changes in patterns of DMARD prescription rates (2000–2005).

Results: There were 2 887 746 prescriptions for DMARDs between August 2000 and June 2005. PBS prescriptions accounted for 95% of these. Government expenditure for the DMARDs was $A156m. Trends in the use of DMARDs remained relatively steady over the study period without a significant change around the time the PBS criteria for biologicals were introduced. Use of hydroxychloroquine and leflunomide increased steadily, use of methotrexate and sulfasalazine was stable and use of gold preparations and penicillamine was considerably lower during this 5‐year period.

Conclusion: Introduction of PBS criteria for access to biologicals did not alter the trends in use of DMARDs based on national dispensing data. This study emphasized the value that would accrue from availability of more comprehensive, de‐identified, individual patient data that would enable more detailed examination of the use of medicines. These data are available, but cannot be easily accessed. It is time to make the data available for approved, ethical research in the interests of better outcomes from medicines supplied under PBS.
Rural Organisation of Acute Stroke Teams project
Authors: Wright A. A. , Ranmuthugala G. , Jones J. , Maydom B. , Disler P.
Published: June 2007

Background: Improving the care of stroke patients is a national priority for the health system in Australia. In rural areas the challenges may be greater. Although best‐practice guidelines for acute and subacute stroke care are well established, their general uptake appears to be limited and implementation strategies are required to promote the use of this evidence‐based care. The Rural Organisation of Australian Stroke Teams (ROAST) project sought to promote the evidence‐based stroke practice in rural hospitals.

Methods: This was a prospective observational project designed to improve the services provided to rural stroke patients, primarily through better organisation of care on general medical wards and emergency departments. Using recognized support strategies, we encouraged the use of nationally recognized key performance indicators and provided audit and feedback of adherence to these indicators to participating hospitals.

Results: Six Victorian hospitals participated in this initial phase of the ROAST project. Information was collected on 348 patients. Ten of the 11 indicators showed greater than 10% improvement in adherence levels and by the end of the project period compared favourably to levels of adherence described in metropolitan hospitals.

Conclusion: The ROAST projected supported a network of clinicians to implement evidence‐based guidelines in acute stroke care in the setting of general medical wards. In doing so, this project has shown that it is quite feasible to deliver best‐practice care to stroke patients in rural Australia.
The impact of reducing the prostate‐specific antigen threshold and including isoform reflex tests on the performance characteristics of a prostate‐cancer detection programme
Authors: Roddam Andrew W. , Hamdy Freddie C. , Allen Naomi E. , Price Christopher P. ,   for the UK Prostate Cancer Risk Management Programme
Published: June 2007

OBJECTIVE

To assess the effects on the performance characteristics, in a prostate‐cancer detection programme using prostate‐specific antigen (PSA) levels, of a lower PSA threshold and the incorporation of reflex (free or complexed PSA) tests.

METHODS

We reviewed publications and extracted data on PSA distributions and performance characteristics of the PSA test and isoform tests from population‐based surveys. We estimated the rate of biopsy, cancers detected, and cancers missed that would result from lowering PSA thresholds and including reflex testing.

RESULTS

Lowering the PSA threshold for biopsy referral to 2 ng/mL would increase the number of referrals from 110 to 230 per 1000 men tested, with most of the extra biopsies being among men with no cancer, i.e. an increase from 74 to 172 per 1000 men tested. However, this increased testing would result in an increase in the cancer‐detection rate from 3.6% to 5.8%. Including a reflex test for men with moderately elevated PSA levels has little effect on programme performance, with only a modest (10–15%) reduction in unnecessary biopsies and a small increase in the numbers of missed cancers.

CONCLUSIONS

Lowering PSA thresholds, with or without the concurrent introduction of reflex tests, would increase both the numbers of cancers detected and the number of patients referred for biopsy procedures, of which most would be unnecessary. As the extra cancers detected are likely to be clinically localized, and with no evidence that their treatment improves the outcome of the disease, such changes place a possibly unjustified additional burden on the healthcare provider.
Bad expression influences time to androgen escape in prostate cancer
Authors: Teo Katy , Gemmell Lisa , Mukherjee Rono , Traynor Pamela , Edwards Joanne
Published: June 2007

OBJECTIVE

To assess the role of selected downstream Bcl‐2 family members (Bad, Bax, Bcl‐2 and Bcl‐xL) in the development of androgen‐independent prostate cancer (AIPC), as androgen‐deprivation therapy is the treatment of choice in advanced prostate cancer, yet patients generally relapse and progress to an AI state within 18–24 months.

PATIENTS, MATERIALS AND METHODS

The patient cohort was established by retrospectively selecting patients with prostate cancer who had an initial response to androgen‐deprivation therapy, but subsequently relapsed with AIPC. In all, 58 patients with prostate cancer were included with matched androgen‐dependent (AD) and AI prostate tumours available for immunohistochemical analysis; two independent observers using a weighted‐histoscore method scored the staining. Changes in Bad, Bax, Bcl‐2 and Bcl‐xL expression during transition to AIPC were evaluated and then correlated to known clinical variables.

RESULTS

High Bad expression in AD tumours was associated with an increased time to biochemical relapse (P = 0.007) and a trend towards improved overall survival (P = 0.053). There were also trends towards a decrease in Bad (P = 0.068) and Bax (P = 0.055) expression with progression to AIPC. There were no significant results for Bcl‐2 or Bcl‐xL.

CONCLUSION

There is evidence to suggest that Bad expression levels at diagnosis influence time to biochemical relapse and overall survival, and that levels of pro‐apoptotic proteins Bad and Bax fall during AIPC development. Bad might therefore represent a possible positive prognostic marker and potential therapeutic target for AIPC in the future.
Increased Akt and phosphorylated Akt expression are associated with malignant biological features of prostate cancer in Japanese men
Authors: Shimizu Yousuke , Segawa Takehiko , Inoue Takahiro , Shiraishi Taizo , Yoshida Toru , Toda Yoshinobu , Yamada Tomomi , Kinukawa Naoko , Terada Naoki , Kobayashi Takashi , Kinoshita Hidefumi , Kamoto Toshiyuki , Nakamura Eijiro , Ogawa Osamu
Published: June 2007

OBJECTIVE

To investigate the relationship between the expression of Akt (a serine/threonine kinase that plays a central role in tumorigenesis), phosphorylated Akt (p‐Akt), prostate cancer tumour grade, androgen receptor (AR)‐staining score, and Ki67 labelling index (LI) in Japanese men.

PATIENTS, MATERIALS AND METHODS

The expression and activation of the cell survival protein Akt was analysed by immunohistochemical staining of paraffin‐embedded tissue microarray sections of prostate carcinoma taken from 52 Japanese men who under radical prostatectomy. The correlation between the expression of Akt and p‐Akt, and their relationship to primary Gleason grade, AR expression and Ki‐67 LI was investigated.

RESULTS

The expression of Akt and p‐Akt were positively related to primary Gleason grade (Fisher’s exact test, P = 0.002 and P = 0.032, respectively). Both AR‐staining score and Ki67 LI were were positively related to the expression of Akt (both P < 0.001) and p‐Akt (P < 0.001 and P = 0.008, respectively). There was a significant positive correlation between the expression of Akt and p‐Akt (Spearman’s correlation, r = 0.644, P < 0.001).

CONCLUSIONS

Increased expression of both Akt and p‐Akt were associated with higher tumour grade as well as a higher AR‐staining score and Ki67 LI. These data indicate that Akt and p‐Akt might be molecular markers for detecting malignant biological features of prostate cancer in the Japanese population.
The use of the interactive whiteboard for creative teaching and learning in literacy and mathematics: a case study
Authors: Wood Ruth , Ashfield Jean
Published: June 2007

This paper considers the ways in which the interactive whiteboard may support and enhance pedagogic practice through whole‐class teaching within literacy and numeracy. Data collected from observations of whole‐class lessons, alongside individual interviews and focus group discussions with class teachers and Initial Teacher Education students, has provided opportunities to consider the potential of such technology to facilitate a more creative approach to whole‐class teaching. The data suggests that, in the first instance, the special features of information and communications technology such as interactivity, ‘provisionality,’ speed, capacity and range enhance the delivery and pace of the session. This research seems to indicate that it is the skill and the professional knowledge of the teacher who mediates the interaction, and facilitates the development of pupils' creative responses at the interface of technology, which is critical to the enhancement of the whole‐class teaching and learning processes.
Integrating Culture in the Design of ICTs
Authors: Young Patricia A.
Published: June 2007

Nationally and internationally, designers are challenged with meeting the needs of diverse populations, and they are faced with the dilemma of how to integrate culture in the design of information and communication technologies (ICTs). This paper reviews the literature in the fields of human–computer interaction and instructional design to argue that the present methods of integrating culture in design serve a limited scope of what culture can be in the design process. Two conclusions were drawn from this research. First, it is apparent that integrating culture in the design of ICTs serves a broader scope, from the generic or culture‐neutral, to the specialised or culture‐specific. Second, this review indicates that design has not caught up with technology and that to create for diverse audiences the process must be deliberate.
Depressive Symptoms in Young Adults: The Influences of the Early Home Environment and Early Educational Child Care
Authors: McLaughlin Andrea E. , Campbell Frances A. , Pungello Elizabeth P. , Skinner Martie
Published: June 2007

The relationship between depressive symptoms in young adults, the quality of the early home environment, and early educational child care was investigated in young adults randomly assigned to receive early childhood intervention in the Abecedarian study. Of the original 111 infants enrolled (98% African American), 104 participated in an age‐21 follow‐up. Those who had early treatment reported fewer depressive symptoms. The protective effects of the early childhood program were further supported by a significant home environment by treatment interaction. Negative effects of lower quality home environments on young adult depressive symptoms were almost entirely offset by preschool treatment, whereas depressive symptoms increased as the quality of the early home environment decreased for those in the control group.
Change in Atypical Maternal Behavior Predicts Change in Attachment Disorganization From 12 to 24 Months in a High‐Risk Sample
Authors: Forbes L. M. , Evans E. M. , Moran G. , Pederson D. R.
Published: June 2007

This longitudinal study examined links between disorganization and atypical maternal behavior at 12 and 24 months in 71 adolescent mother–child dyads. Organized attachment and maternal not disrupted behavior were more stable than disorganization and disrupted behavior, respectively. At both ages, disorganization and maternal disrupted behavior were significantly correlated. Change in atypical maternal behavior predicted change in disorganization across time. The results provide substantial support for extant theories linking anomalous maternal behavior to the development of disorganized attachment. The Interesting‐but‐Scary paradigm, introduced in this study, promises to be a useful tool for assessing attachment and maternal behavior in toddlerhood.
Why are Hyperactivity and Academic Achievement Related?
Authors: Saudino Kimberly J. , Plomin Robert
Published: June 2007

Although a negative association between hyperactivity and academic achievement is well documented, little is known about the genetic and/or environmental mechanisms responsible for the association. The present study explored links between parent and teacher ratings of hyperactive behavior problems and teacher‐assessed achievement in a sample of 1,876 twin pairs (mean age 7.04 years). The results did not differ across rater, nor were there significant differences between males or females or for twins in the same or different classrooms. Hyperactivity was significantly correlated with achievement. Multivariate model‐fitting analyses revealed significant genetic and nonshared environmental covariance between the two phenotypes. In addition, bivariate heritabilities were substantial, indicating that the phenotypic correlations between hyperactivity and achievement were largely mediated by genetic influences.
China: Coming to Grips with the New Global Player
Authors: Siebert Horst
Published: June 2007

This paper analyses China's economic performance in the last 25 years and discusses its prospect for growth in the future. Exports and investment have been the two driving forces for the high annual GDP growth rates. FDI plays an important role. However, structural issues such as the loss‐making state‐owned firms and the fragile banking industry have to be solved. Monetary policy is complicated by the accumulation of reserves which, however, provide an insurance for the fragile banking system. Property rights, a crucial element in transforming a communist society, are far from being clearly developed. Major policy issues in the future include the correction of the distorted growth process and of the institutional deficits, especially with respect to the rule of law and the lack of democracy.