bluuebunny/crossref_metadata_2025 huggingface dataset:
Vector status of three leafhopper species for Australian lucerne yellows phytoplasma
Authors: Pilkington Leigh J , Gurr Geoff M , Fletcher Murray J , Nikandrow Alex , Elliott Eric
Published: November 2004

Abstract  The leafhoppers Orosius argentatus (Evans), Austroagallia torrida (Evans) and Batracomorphus angustatus (Osborn) were used in transmission tests to determine their vector status for the phytoplasma associated with Australian lucerne yellows (ALuY). Caged, seed‐grown lucerne plants were monitored for foliar symptom expression after feeding by leafhoppers transferred from ALuY symptomatic lucerne plants. Twelve of 25 plants developed phytoplasma disease‐like symptoms including stunting and yellowing. The most pronounced foliar symptoms were displayed by five plants that had been fed on by O. argentatus and four plants that had been fed on by A. torrida. One plant, fed on by O. argentatus, showed the distinctive root symptoms of ALuY. A phytoplasma was identified by electron microscopy in two plants fed on by O. argentatus and one by A. torrida. For each group of plants that had been fed on by a single leafhopper species, one plant was phytoplasma positive as determined by the polymerase chain reaction (PCR) using universal primers. The phytoplasma detected by PCR in the plant fed on by A. torrida was identified by restriction fragment length polymorphism (RFLP) analysis as the tomato big bud (TBB) phytoplasma. The PCR product from two plants fed on by B. angustatus and O. argentatus were too faint for RFLP analysis. PCR assays were conducted on DNA extracted from the head and thorax of each leafhopper species from transmission tests and from field‐collected insects, but no phytoplasma DNA was detected. These findings suggest O. argentatus is a vector of the ALuY pathogen and A. torrida is a vector of the TBB phytoplasma.
Impact of selective cyclooxygenase‐2 inhibitors on anti‐ulcer medication and non‐steroidal anti‐inflammatory drug use in patients with rheumatic disease
Authors: Joshua F. F. , Oakley S. P. , Major G. A.
Published: November 2004

Abstract

Background : Anti‐inflammatory medications are the most common treatment for rheumatic disease in Australia. Recent years have seen large increases in the use of selective cyclooxygenase‐2 (COX‐2) inhibitors. Predictors of use, costs and benefits of the new medications have not been evaluated.

Aims : To determine trends in selective COX‐2 inhibitor, non‐steroidal anti‐inflammatory drug (NSAID) and anti‐ulcer medication (AUM) prescription following the introduction of selective COX‐2 inhibitors; to determine predictors of selective COX‐2 inhibitor, NSAID and AUM prescribing and to perform a limited evaluation of the costs and benefits associated with the introduction of selective COX‐2 inhibitors.

Methods : Groups of consecutive patients attending a hospital rheumatology clinic, private rooms of consulting rheumatologists and a dermatology outpatient clinic were surveyed by investigator‐administered questionnaire on three separate occasions. Information was sought about AUM, NSAID and selective COX‐2 use and about factors likely to influence selective COX‐2 prescribing. Sampling was carried out at 3, 10 and 16 months after the release of COX‐2 selective inhibitors in Australia. The final survey was 3 months after Pharmaceutical Benefits Scheme (PBS) listing of celecoxib in Australia. Costs of treatment were calculated from survey findings of frequency of drug use as well as published drug prices and hospitalisation costs.

Results : Four‐hundred and fifty‐eight patients were surveyed. From the 3 months post‐release to the 3 months post‐PBS listing, a period of 13 months, COX‐2 use in rheumatology patients increased from 18 to 57%. De novo prescription of selective COX‐2 inhibitors increased from 42 to 61%. During the same period there was a fall in both NSAID (43−20%) and AUM use (41−27%). Neither selective COX‐2 inhibitor nor NSAID prescription was related to risk factors for gastro­intestinal (GI) complications, but AUM use was found to correlate strongly to histories of gastroscopy, GI ulceration or GI bleed. The calculated increase in the cost of treatment was $1 033 002/10 000 patients per year. The net cost per serious GI event prevented was $71 736, compared with the normal cost of treatment of $2004.

Conclusions : Among rheumatology patients, selective COX‐2 inhibitors have largely replaced NSAIDs and have resulted in a reduction in AUM consumption, but prescribing patterns for selective COX‐2 inhibitors have not been related clearly to risk factors for GI compli­cations. The introduction of selective COX‐2 inhibitors has been associated with a significant increase in expenditure. (Intern Med J 2004; 34: 153−161)
Impact of hydroxychloroquine therapy on chronic urticaria: chronic autoimmune urticaria study and evaluation
Authors: Reeves G. E. M. , Boyle M. J. , Bonfield J. , Dobson P. , Loewenthal M.
Published: November 2004

Abstract

Background:  Chronic urticaria (CU) imposes profound impairment on quality of life. Up to 60% of idiopathic CU is associated with autoimmune phenomena, and may respond to immunomodulation. Hydroxychloroquine offers potential efficacy for CU and is relatively benign compared with most other therapeutic approaches.

Objective:  The aim of the chronic autoimmune urticaria study and evaluation was to evaluate the efficacy of hydroxychloroquine in patients with chronic idiopathic urticaria.

Methods:  Twenty‐one patients referred to the Immunology and Allergy Unit at John Hunter Hospital, New South Wales, Australia, with idiopathic CU were randomised to receive treatment with standard urticaria therapies (corticosteroids, H2‐antihistamines, H1‐­antihistamines, doxepin) with or without hydroxychloroquine. Markers of autoimmunity, thyroid disease and mast‐cell autoreactivity (autologous serum skin‐prick testing (ASPT)) were assessed. Measures of urticaria control were compared at baseline and at 12 weeks for the 18 individuals who completed the study. These included urticaria scores, medication scores and quality‐of‐life indices.

Results:  The hydroxychloroquine‐treated group achieved significant improvements in quality of life as assessed by the global symptom severity score and the LAMY‐7 (a quality of life index designed by Lamy, 7th revision) at 12 weeks (P < 0.01 and P < 0.05, respectively). No significant treatment effect on medication requirements or urticaria score was detected, although differences between treatment groups approached statistical significance for urticaria score and medication requirements (0.05 < P < 0.10). ASPT‐reactivity did not correlate to hydroxychloroquine‐responsiveness. Hydroxychloroquine was well tolerated.

Conclusion:  Immunomodulation with hydroxychloroquine is safe and appears to offer some efficacy as an intervention in CU. (Intern Med J 2004; 34: 182−186)
The Wellcome Trust in Australasia: return on investment
Authors: Whitworth J. A. , Phillips M. , Jack J.
Published: November 2004

Abstract

The Wellcome Trust is the world's largest medical research charity. Investment by the Trust in research in Australia and New Zealand has contributed very substantially to local research capacity through support of people, equipment and programmes. Further, the Trust's funding has ­successfully leveraged additional investment from both government and charitable foundations. Current initiatives are focused on development of research partnerships between Australasia and our regional neighbours. (Intern Med J 2004; 34: 211−214)
Clinical features in the emergency department can identify patients with suspected acute coronary syndromes who are safe for care in unmonitored hospital beds
Authors: Kelly A.‐M. , Kerr D.
Published: November 2004

Background: Standard practice for patients requiring hospital admission with suspected acute coronary syndromes (ACS) is admission to a monitored cardiology bed. The Western Hospital Chest Pain Protocol was developed to identify a subset of these patients who could be safely managed in an unmonitored bed.

Aim: The objective of this prospective study of chest pain patients classified as ‘high’ or ‘intermediate’ risk by the Agency for Health Care Policy and Research/National Health and Medical Research Council guidelines was to further evaluate the safety of this protocol.

Methods: This study was a prospective, observational, cohort study investigating the outcomes of patients admitted to hospital with suspected ACS. The primary outcome of interest was death or life‐threatening arrhythmia within 24 h of hospital admission.

Results: If the Western Hospital Chest Pain Protocol had been strictly applied, there would have been one death in the group assigned to unmonitored beds (1/750; 0.13%, 95% confidence interval 0.01−0.85%) and no other life‐threatening arrhythmias.

Conclusion: There is a subgroup of patients with suspected ACS who require hospital admission who can, based on clinical and biochemical features in the emergency department, be safely assigned to unmonitored beds. (Intern Med J 2004; 34: 594−597)
Unobvious wounds: the suffering of hospice patients
Authors: Terry W. , Olson L. G.
Published: November 2004

Background:  The suffering of palliative care patients is ordinarily thought of in terms of symptoms, and these are identified by medical terms (pain, nausea, depression). The problematic issue of relief of patients’ pain meaning the same thing as the ‘relief of the suffering and distress of terminally ill patients’ has been raised.

Aim:  The aim of this study was to estimate the frequency with which medically defined suffering matched the reported suffering of our patients.

Methods:  One hundred patients admitted to a hospice were asked ‘In what way are you suffering?’ The patients’ diagnoses, their pain scores and the reasons for admission as defined by the treating clinicians were recorded. The mean age of the patients was 68 years (range 28−93 years), 92 had advanced malignant disease and 51 were women.

Results:  Twenty‐four patients were unable to state the reason for hospice admission, but none had any uncertainty in identifying the nature of their own suffering. There was a weak correlation between the patient's view of their suffering and the reason for admission. The identification of pain as the cause of suffering was weakly correlated with pain scores. Some patients with pain scores of 8−10/10 did not mention pain as a cause of suffering, and others with scores of 0/10 did identify pain as the cause of suffering.

Conclusion:  Asking hospice patients about suffering in a simple open‐ended way can expose a different dimension of distress, and the views of the 100 patients of this study support the statement that relief of pain and relief of suffering are not the same. (Intern Med J 2004; 34: 604−607)
Trust and confidence: towards mutual acceptance of ethics committee approval of multicentre studies
Authors: Sarson‐Lawrence M. , Alt C. , Mok M. T. , Dodds M. , Rosenthal M. A.
Published: November 2004

Aims:  To compare issues raised by Human Research Ethics Committees (HREC) during the ethics review process and to determine the length of time taken to gain HREC approval for multicentre research studies.

Methods:  Review and analysis of HREC documentation and correspondence for all multicentre research studies were conducted through three HREC under the auspices of Cancer Trials Australia, Melbourne, Victoria, Australia, between November 1997 and March 2001 to determine the variance of documentation, correspondence and recommendations across the three HREC and the time taken for study approval.

Results:  Thirty‐one projects were submitted to any two of the HREC (16 studies) or all three HREC (15 studies). The median time for study approval at an individual HREC was 75 days, but it was 111 days for approval at all participating sites. There were 554 clarifications or comments made by the reviewing HREC, the majority of which had no significant bearing on the ethical or scientific calibre of the study. There was only one study in which a significant protocol change was requested by a HREC.

Conclusions:  Multicentre study approvals are delayed when submitted to multiple HREC. The three HREC raised similar issues without substantive differences in their recommendations. A process for the mutual acceptance of HREC recommendations could facilitate multicentre research. (Intern Med J 2004; 34: 598−603)
Input and frequency‐specific entrainment of postsynaptic firing by IPSPs of perisomatic or dendritic origin
Authors: Tamás Gábor , Szabadics János , Lörincz Andrea , Somogyi Peter
Published: November 2004

Correlated activity of cortical neurons underlies cognitive processes. Networks of several distinct classes of γ‐aminobutyric acid (GABA)ergic interneurons are capable of synchronizing cortical neurons at behaviourally relevant frequencies. Here we show that perisomatic and dendritic GABAergic inputs provided by two classes of GABAergic cells, fast spiking and bitufted interneurons, respectively, entrain the timing of postsynaptic spikes differentially in both pyramidal cells and interneurons at beta and gamma frequencies. Entrainment of pyramidal as well as regular spiking non‐pyramidal cells was input site and inhibitory postsynaptic potential frequency dependent. Gamma frequency input from fast spiking cells entrained pyramidal cells on the positive phase of an intrinsic cellular theta oscillation, whereas input from bitufted cells was most effective in gamma frequency entrainment on the negative phase of the theta oscillation. The discharge of regular spiking interneurons was phased at gamma frequency by dendritic input from bitufted cells, but not by perisomatic input from fast spiking cells. Action potentials in fast spiking GABAergic neurons were phased at gamma frequency by both other fast spiking and bitufted cells, regardless of whether the presynaptic GABAergic input was at gamma or beta frequency. The interaction of cell type‐specific intrinsic properties and location‐selective GABAergic inputs could result in a spatio‐temporally regulated synchronization and gating of cortical spike propagation in the network.
Involvement of corticostriatal glutamatergic terminals in striatal dopamine release elicited by stimulation of δ‐opioid receptors
Authors: Billet Fabrice , Dourmap Nathalie , Costentin Jean
Published: November 2004

We have previously shown that striatal dopamine release induced locally by a δ‐opioid receptor agonist was totally inhibited by a glutamate N‐methyl‐d‐aspartate receptor antagonist, indicating the involvement of glutamatergic receptors in this effect. The aim of the present study was to specify this mechanism. Firstly, we investigated the effect of [D‐Pen2,D‐Pen5]‐enkephalin (DPDPE) on glutamate release in rats by intrastriatal microdialysis. The infusion of DPDPE (10 µm) enhanced the glutamate content in dialysate by approximately 34%, an effect which did not appear to result from inhibition of glutamate uptake. We then considered the consequences of a unilateral thermocoagulation of the frontal cortex on either glutamate or dopamine release induced by stimulation of δ‐opioid receptors 2 days later. This lesion, which decreased the glutamate content in ipsilateral striatum by approximately 30%, totally prevented the increase in dialysate levels of glutamate induced by DPDPE. Moreover, whereas DPDPE (10 µm) was found to increase the striatal dopamine release in intact animals by approximately 59%, this effect was also completely suppressed by the cortical lesion. Finally, we studied the effect of the lesion on the [3H]‐DPDPE binding to striatal membranes prepared from the whole striatum. In the ipsilateral striatum a significant decrease in this [3H]‐DPDPE binding (by approximately 18%) was found 2 days after the lesion. Our results indicate that the increase in striatal dopamine release induced by DPDPE probably depends on glutamate release from corticostriatal glutamatergic afferents in response to the stimulation of δ‐opioid receptors located on terminals of these neurons.
The extracellular matrix glycoprotein Tenascin‐C is expressed by oligodendrocyte precursor cells and required for the regulation of maturation rate, survival and responsiveness to platelet‐derived growth factor
Authors: Garwood Jeremy , Garcion Emmanuel , Dobbertin Alexandre , Heck Nicolas , Calco Valerie , Ffrench‐Constant Charles , Faissner Andreas
Published: November 2004

Analysis of Tenascin‐C (TN‐C) knockout mice revealed novel roles for this extracellular matrix (ECM) protein in regulation of the developmental programme of oligodendrocyte precursor cells (OPCs), their maturation into myelinating oligodendrocytes and sensitivity to growth factors. A major component of the ECM of developing nervous tissue, TN‐C was expressed in zones of proliferation, migration and morphogenesis. Examination of TN‐C knockout mice showed roles for TN‐C in control of OPC proliferation and migration towards zones of myelination [E. Garcion et al. (2001) Development, 128, 2485–2496]. Extending our studies of TN‐C effects on OPC development we found that OPCs can endogenously express TN‐C protein. This expression covered the whole range of possible TN‐C isoforms and could be strongly up‐regulated by leukaemia inhibitory factor and ciliary neurotrophic factor, cytokines known to modulate OPC proliferation and survival. Comparative analysis of TN‐C knockout OPCs with wild‐type OPCs reveals an accelerated rate of maturation in the absence of TN‐C, with earlier morphological differentiation and precocious expression of myelin basic protein. TN‐C knockout OPCs plated on poly‐lysine displayed higher levels of apoptosis than wild‐type OPCs and there was also an earlier loss of responsiveness to the protective effects of platelet‐derived growth factor (PDGF), indicating that TN‐C has anti‐apoptotic effects that may be associated with PDGF signalling. The existence of mechanisms to compensate for the absence of TN‐C in the knockout is indicated by the development of oligodendrocytes derived from TN‐C knockout neurospheres. These were present in equivalent proportions to those found in wild‐type neurospheres but displayed enhanced myelin membrane formation.
Nucleus accumbens neurons in the rat exhibit differential activity to conditioned reinforcers and primary reinforcers within a second‐order schedule of saccharin reinforcement
Authors: Wilson David I. G. , Bowman Eric M.
Published: November 2004

The nucleus accumbens has been associated with processing information related to primary reinforcement and reward. Most neurophysiological studies report that nucleus accumbens neurons are phasically excited in response to the onsets of salient events during the seeking of reinforcement and to the delivery of primary reinforcers. However, a minority of studies report inhibition during primary reinforcement. We recorded from 65 neurons in the nucleus accumbens whilst thirsty rats performed under a second‐order schedule of saccharin reinforcement. This allowed us to analyse neural activity and behaviour during reinforcer‐seeking in the presence of conditioned reinforcers (second‐order stimuli, also called ‘conditioned stimuli’), and during primary reinforcer consumption. Specifically, we sought to examine the valence of potential neural responses to primary reinforcement, to compare these responses to second‐order stimulus‐evoked responses, and to determine whether responses were differential to second‐order stimuli presented at different time points within the schedule. Fifty out of 65 neurons we sampled responded to the second‐order stimulus and/or consumption of the primary reinforcer. Most neurons in our sample exhibited excitation following the second‐order stimulus and inhibition to the primary reinforcer, a pattern also present over the average response of the neural population. However, there was no systematic variation in neural responses evoked by second‐order stimuli presented at different temporal proximities to primary reinforcement. Our results provide evidence that partially overlapping mechanisms within the nucleus accumbens differentially process conditioned reinforcers and primary reinforcers.
Putative NMDA receptors in Hydra: a biochemical and functional study
Authors: Pierobon Paola , Sogliano Cristiana , Minei Rosario , Tino Angela , Porcu Patrizia , Marino Giuseppe , Tortiglione Claudia , Concas Alessandra
Published: November 2004

The feeding behaviour of the freshwater polyp Hydra vulgaris (Cnidaria, Hydrozoa) is modulated by a number of molecules acting as neurotransmitters in other nervous systems. Here we present biochemical and functional evidence of the occurrence of putative NMDA receptors in Hydra tissues. Saturation experiments showed the presence of one population of binding sites with nanomolar affinity and low capacity for [3H]MK‐801. Before equilibrium, [3H]MK‐801 binding was increased by the agonists glutamate and glycine as well as by reduced glutathione (GSH). In vivo the glutamate receptor agonist NMDA markedly decreased the duration of the response to GSH. This effect was linearly related to ligand doses in the nanomolar concentration range and was counteracted by either the NMDAR‐specific antagonist D‐AP5 or by the d‐serine antagonist DCKA. When NMDA concentration was increased to 10 or 100 µm, duration of the response to GSH was no longer affected unless the lectin concanavalin A, which prevents receptor desensitization in other systems, was added to the test medium. Simultaneous administration of ineffective doses of NMDA and strychnine, glycine or d‐serine, an agonist at the glycine binding site of the NMDA receptor in vertebrate CNS, resulted in a strong reduction of response duration. Both D‐AP5 and DCKA suppressed this effect. These results, together with the decrease in response duration produced by d‐serine, support the hypothesis that NMDA‐like glutamate receptors may occur in Hydra tissues where they are involved in modulation of the response to GSH with opposite actions to those of GABA and glycine.
Peripherally inserted central venous catheters in preterm newborns: two unusual complications
Authors: Pigna A. , Bachiocco V. , Fae M. , Cuppini F.
Published: November 2004

This report describes the case of two newborns who suffered unusual complications after peripheral insertion of a central venous catheter. In one baby a fragment of the catheter tip became embolized in a peripheral branch of the left pulmonary artery. In the other baby, the catheter perforated a peripheral branch of the pulmonary artery, giving rise to chemical pneumonitis with extensive pleural effusion. The outcome was positive for both babies. A large clinical series is necessary to establish the complications of this procedure, their prevention and management.
Anaesthetic experiences in three sets of conjoined twins in King Chulalongkorn Memorial Hospital
Authors: Leelanukrom Ruenreong , Somboonviboon Wanna , Bunburaphong Pavena , Kiatkungwanklai Predee
Published: November 2004

We describe the anaesthetic management for magnetic resonance image scanning, angiography and surgical operations in three sets of conjoined twins (ischiopagus, throracopagus and pygopagus) in King Chulalongkorn Memorial Hospital during 1996–2002. The anaesthetic technique and associated problems are summarized.
Unexpectedly high clonal diversity of two salt marsh perennials across a severe environmental gradient
Authors: Richards Christina L. , Hamrick J. L. , Donovan Lisa A. , Mauricio Rodney
Published: November 2004

In salt marsh habitats, noted for their extreme environments, a widely held assumption is that a few large clones dominate plant populations. Using a large number of polymorphic genetic markers, we were able to test this assumption for two salt marsh plants known to span extreme salinity gradients. For both species, clonal diversity was surprisingly high across populations: Simpson's diversity indices were 0.96 and 0.99. Although clonal diversity was high, there was no pattern of association between specific clones or alleles with salt microhabitat. Our findings suggest that sexual reproduction and recruitment from seeds may have been generally underappreciated as an important ecological force in the salt marsh. Furthermore, clonal diversity has implications for conservation and restoration of these critical coastal habitats, particularly with regard to buffering environmental change or disease. Recent studies also suggest that high levels of intraspecific diversity can affect a variety of community and ecosystem processes.
The coincidence of rarity and richness and the potential signature of history in centres of endemism
Authors: Jetz Walter , Rahbek Carsten , Colwell Robert K.
Published: November 2004

We investigate the relative importance of stochastic and environmental/topographic effects on the occurrence of avian centres of endemism, evaluating their potential historical importance for broad‐scale patterns in species richness across Sub‐Saharan Africa. Because species‐rich areas are more likely to be centres of endemism by chance alone, we test two null models: Model 1 calculates expected patterns of endemism using a random draw from the occurrence records of the continental assemblage, whereas Model 2 additionally implements the potential role of geometric constraints. Since Model 1 yields better quantitative predictions we use it to identify centres of endemism controlled for richness. Altitudinal range and low seasonality emerge as core environmental predictors for these areas, which contain unusually high species richness compared to other parts of sub‐Saharan Africa, even when controlled for environmental differences. This result supports the idea that centres of endemism may represent areas of special evolutionary history, probably as centres of diversification.
Nitrogen deposition and plant species interact to influence soil carbon stabilization
Authors: Dijkstra Feike A. , Hobbie Sarah E. , Knops Johannes M. H. , Reich Peter B.
Published: November 2004

Anthropogenic nitrogen (N) deposition effects on soil organic carbon (C) decomposition remain controversial, while the role of plant species composition in mediating effects of N deposition on soil organic C decomposition and long‐term soil C sequestration is virtually unknown. Here we provide evidence from a 5‐year grassland field experiment in Minnesota that under elevated atmospheric CO2 concentration (560 ppm), plant species determine whether N deposition inhibits the decomposition of soil organic matter via inter‐specific variation in root lignin concentration. Plant species producing lignin‐rich litter increased stabilization of soil C older than 5 years, but only in combination with elevated N inputs (4 g m−2 year−1). Our results suggest that N deposition will increase soil C sequestration in those ecosystems where vegetation composition and/or elevated atmospheric CO2 cause high litter lignin inputs to soils.
Long‐term results of a self‐expanding wallstent in the treatment of urethral stricture
Authors: Hussain Mahreen , Greenwell Tamsin J. , Shah Julian , Mundy Anthony
Published: November 2004

OBJECTIVE

To report the long‐term outcome over 12 years of using the urethral UrolumeTM wallstent (AMS, Minnetonka, MI, USA) for treating recurrent bulbar urethral stricture disease.

PATIENTS AND METHODS

The case‐notes of 60 consecutive men with urethral Urolume wallstents placed for treating recurrent bulbar strictures were reviewed retrospectively. Information was collected on patient demographics, stricture aetiology, stent‐related complications and the need for further surgery to treat stent‐ or stricture‐related complications.

RESULTS

The mean (range) age of the men was 58 (32–76) years. The most common cause of stricture was iatrogenic, arising after previous endoscopic surgery or after an indwelling catheter (45%). Thirty‐five men had complications, with re‐operation required in 27 (45%) of them. The most frequent nonsurgical complications were post‐micturition dribble (32%) and recurrent urinary tract infections (27%). The most common surgical interventions required were transurethral resection of obstructing stent hyperplasia (32%), urethral dilatation or urethrotomy for stent obstruction or stricture (25%) and endoscopic litholapaxy for stent encrustation or stone (17%).

CONCLUSIONS

The Urolume wallstent should only be used in patients who are unfit for or who refuse a bulbar urethroplasty.
Comparison of survival following coronary artery bypass grafting vs. percutaneous coronary intervention in diabetic and non‐diabetic patients: retrospective cohort study of 6320 procedures
Authors: Pell J. P. , Pell A. C. H. , Jeffrey R. R. , Jennings K. , Oldroyd K. , Eteiba H. , Hogg K. J. , Murday A. , Faichney A. , Colquhoun I. , Berg G. , Starkey I. R. , Flapan A. , Mankad P.
Published: November 2004

Aim  To determine whether mortality following percutaneous coronary intervention vs. coronary bypass grafting varies according to whether or not patients have diabetes.

Methods  We used the Scottish Coronary Revascularization Register to identify all patients undergoing revascularization in Scottish NHS hospitals since 1997. We excluded single‐vessel disease, left main stem stenosis, and bypass grafting performed at the same time as other operations. We used death certificate data from the Registrar General to identify all subsequent deaths.

Results  Of the 6320 eligible procedures, 5042 (80%) were bypass grafts and 1278 (20%) angioplasties. Overall 831 (13%) patients had diabetes with no significant difference by procedure (13% vs. 12%). A total of 382 deaths occurred over a mean follow‐up of 2.3 years. Diabetic patients had a poorer prognosis following both surgery (adjusted hazards ratio (HR) 1.43, 95% confidence interval (CI) 1.08, 1.89) and percutaneous intervention (adjusted HR 2.58, 95% CI 1.43, 4.63). Among non‐diabetic patients, no significant differences in mortality were detected between the two procedures. Among diabetic patients, no significant difference was detected in those with two‐vessel disease. In those with impaired left ventricular function and triple‐vessel disease, angioplasty was associated with a significantly higher risk of death (adjusted HR 3.58, 95% CI 1.40, 9.19).

Conclusions  This is the first study to demonstrate statistically significant results that support the BARI trial findings. Our study demonstrated a significant difference for triple‐vessel disease but not two‐vessel disease. The former may be due to incomplete revascularization using percutaneous intervention. Our results require corroboration from randomized trials.
Evaluation of a bedside blood ketone sensor: the effects of acidosis, hyperglycaemia and acetoacetate on sensor performance
Authors: Khan A. S. A. , Talbot J. A. , Tieszen K. L. , Gardener E. A. , Gibson J. M. , New J. P.
Published: November 2004

Aims  To assess the performance of a handheld bedside ketone sensor in the face of likely metabolic disturbances in diabetic ketoacidosis, namely: pH, glucose and acetoacetate.

Methods  The effects of pH (7.44–6.83), glucose (5–50 mmol/l) and acetoacetate (0–5 mmol/l) were examined in venous blood to investigate the accuracy of betahydroxybutyrate measurement (0–5 mmol/l) by a handheld ketone sensor. Sensor results were compared with a reference method. Linear regression models were fitted to the difference between the methods with the concentration of metabolite as the explanatory factor.

Results  Decreasing pH and increasing glucose had no effect on the accuracy of the handheld ketone sensor; the gradients of the fitted lines were −0.14 and −0.003, respectively. The 95% confidence intervals were −0.7–0.4 and −0.01–0.004, respectively (P = 0.59 and 0.4, respectively). In the acetoacetate study, a positive relationship between the sensor and reference method results was found, the gradient was 0.09. The 95% confidence interval was 0.05–0.14 (P ≤ 0.001), indicating that high concentrations of acetoacetate interfere with the sensor performance.

Conclusions  Acidosis and hyperglycaemia have minimal effects on the sensor performance. However, high concentrations of acetoacetate result in some overestimation of betahydroxybutyrate. This bedside ketone sensor provides useful data over a broad range of conditions likely to be encountered during moderate to severe diabetic ketoacidosis.
Independent association of uric acid levels with peripheral arterial disease in Taiwanese patients with Type 2 diabetes
Authors: Tseng C.‐H.
Published: November 2004

Aims  Hyperuricaemia may be a risk factor for atherosclerotic disease. Its association with peripheral arterial disease (PAD) has not been studied in Taiwanese patients with Type 2 diabetes.

Methods  Uric acid (UA) levels and PAD were evaluated in 508 Taiwanese outpatients with Type 2 diabetes (210 men, 298 women; mean age ± sd, 63.8 ± 10.6 years). PAD was diagnosed when the ankle‐brachial index was < 0.9. Patients with an ankle‐brachial index of ≥ 1.3 were excluded because of possible medial arterial calcification. Potential confounding variables with P < 0.10 were adjusted for in multivariate analyses.

Results  In univariate analyses, UA levels were higher in patients with PAD than in those without PAD (345.0 ± 95.2 vs. 309.3 ± 89.2 µmol/l; P < 0.0005). Prevalences of PAD for quintiles of UA levels were 6.8, 8.9, 10.2, 13.1 and 16.5%, respectively (P‐trend < 0.05). With UA level as a continuous variable, the multivariate‐adjusted odds ratio (95% confidence interval) for PAD was 1.005 (1.001–1.008) (P < 0.01). The optimal cut‐off point for UA as determined by the receiver operating characteristic curve was 264.7 µmol/l. The sensitivity and specificity at this cut‐off point was 82.6 and 33.3%, respectively. The area under curve was 0.60 (95% confidence interval: 0.53–0.68). The multivariate‐adjusted odds ratio for PAD for UA above this level was 2.736 (1.239–6.043) (P < 0.05). The results after excluding 56 cases using diuretics were similar.

Conclusions  Elevated uric acid level is a significant and independent risk factor for PAD in Taiwanese patients with Type 2 diabetes.
Inhaled micronized crystalline human insulin using a dry powder inhaler: dose‐response and time‐action profiles1
Authors: Rave K. , Nosek L. , Heinemann L. , Gonzales C. , Ernest C. S. , Chien J. , Muchmore D.
Published: November 2004

Aim  The aim of this euglycaemic glucose clamp study was to investigate the pharmacokinetics, glucodynamics, safety and tolerability of micronized crystalline human insulin inhalation powder delivered by a Spiros® dry powder inhaler system in healthy volunteers.

Methods  Thirteen healthy, non‐smoking, male and female volunteers [age 30 ± 7 years; BMI 23.5 ± 2.7 kg/m2; (mean ± sd)] with normal pulmonary function participated in an open‐label, randomised, 6‐period crossover trial. Each volunteer received four single doses of inhaled insulin (60, 90, 120, 150 U) on separate occasions. For comparison, each volunteer also received two of three possible doses of subcutaneous (s.c.) injected regular human insulin (8, 14, or 20 U).

Results  Serum immunoreactive insulin following inhalation of insulin peaked an average of 60 min earlier compared with s.c. injected insulin (P < 0.0001). Following inhalation, the time to maximum glucose infusion rate occurred an average of 70 min earlier than with s.c. insulin: 187, 129, 161 and 162 min vs. 227, 241 and 241 min (P < 0.0001). The dose‐response relationships for serum insulin pharmacokinetics and glucodynamics were linear for both inhaled and s.c. insulin. Relative bioavailability (based on serum insulin levels) ranged from 11.5 to 12.2% for the four doses of inhaled insulin and relative biopotency (based on glucose infusion rates) was 10.0 to 16.5%, respectively. Dosing was well tolerated by all volunteers.

Conclusion  This study demonstrates that inhalation of human insulin via a dry powder inhaler system provides a promising alternative route for administration of insulin.
Introduction of IFCC reference method for calibration of HbA1c: implications for clinical care
Authors: Manley S. , John W. G. , Marshall S.
Published: November 2004

HbA1c is recommended for monitoring glycaemic control and quantifying the risk of complications in patients with diabetes. National guidelines for treatment of patients with diabetes in UK specify that HbA1c measurements should be Diabetes Control and Complications Trial (DCCT)‐aligned i.e. comparable to the DCCT and UK Prospective Diabetes Study (UKPDS).

The IFCC reference method for HbA1c will be introduced in Europe in December 2003 for calibration of all laboratory and POCT (point of care testing) methods for HbA1c following the recent EC ‘In Vitro Diagnostic’ (IVD) directive. This reference method involves measurement of HbA1c and HbA0 by electron‐spray ionisation‐mass spectrometry or capillary electrophoresis with the reference range approximately 2% HbA1c lower than the corresponding range from the DCCT. However, this EC IVD directive will not change reporting of DCCT‐aligned HbA1c in the UK.

Professionals involved in the care of patients with diabetes in the UK met with Dr Sue Roberts in London in July 2003. It was decided that in the UK DCCT‐aligned HbA1c will continue to be reported from December 2003 for patient care and that laboratories currently reporting non‐aligned DCCT HbA1c should change to reporting DCCT‐aligned results as soon as possible. It was considered important for diabetes care in the UK that the reporting of HbA1c should not fragment. The UK HbA1c Standardization Committee was set up to hold ‘a watching brief’ on HbA1c especially with relation to reporting of HbA1c in other countries.
Taste the difference, make the difference: the role of a public health nutritionist in the UK food retail industry and a rural community in Zambia
Authors: Richards S.
Published: November 2004

Summary  Nutritionists and Dietitians have an important role to play in enabling populations to improve their health. Using examples from a UK food retailer and rural community in Zambia, this article highlights the importance of developing strong partnerships which support sustainable community‐based activities that promote healthier practices at the individual, family and community levels.
Estimation methods for stochastic volatility models: a survey
Authors: Broto Carmen , Ruiz Esther
Published: November 2004

Abstract.  Although stochastic volatility (SV) models have an intuitive appeal, their empirical application has been limited mainly due to difficulties involved in their estimation. The main problem is that the likelihood function is hard to evaluate. However, recently, several new estimation methods have been introduced and the literature on SV models has grown substantially. In this article, we review this literature. We describe the main estimators of the parameters and the underlying volatilities focusing on their advantages and limitations both from the theoretical and empirical point of view. We complete the survey with an application of the most important procedures to the S&P 500 stock price index.
A ‘European’ Conception of Legal Consciousness: Rediscovering Eugen Ehrlich
Authors: Hertogh Marc
Published: November 2004

This paper discusses the present ‘legal consciousness’ literature and seeks to identify two different conceptions of legal consciousness. Most of this literature originated in the United States, but there has also been a growing interest in issues of legal consciousness in Europe. The use of the term ‘legal consciousness ’ in these European discussions is, however, remarkably different from its use in the United States literature. It is argued that the most commonly used ‘American ’ conception of legal consciousness reflects important ideas of Roscoe Pound and asks: how do people experience (official) law? By contrast, a European conception of legal consciousness, which was first introduced by the Austrian legal theorist Eugen Ehrlich, focuses on: what do people experience as ‘law ’? After both perspectives are applied in a case‐study of a run‐down neighbourhood in the Netherlands, it is concluded that future studies of legal consciousness may benefit from an integration of the two conceptions.
Marriage and the Moral Bases of Personal Relationships
Authors: Eekelaar John , Maclean Mavis
Published: November 2004

Marriage is a legal institution. Current debates about whether it should be extended beyond its traditional heterosexual constitution, and whether many of its legal incidents should apply to couples who live together without marrying, and about the introduction of civil partnership (modelled closely on marriage) for same‐sex couples, make an examination of its contemporary role particularly timely. This article is about the interplay between the institution of marriage and ideas of obligation within personal relationships. It takes as its starting point some commonly held opinions. First, that the sense of obligation which hitherto guided people's behaviour in their personal relationships has much diminished or even disappeared. Second, that this diminution is reflected in the decline in marriage. We will then examine what the evidence of an empirical study conducted by the Oxford Centre for Family Law and Policy reveals about the way people in married and unmarried relationships understand the nature of their personal obligations. In doing this it will be seen that the moral bases which underpin people's personal relationships is complex and does not correspond in a simple way with formal, external social categories.
Efficiency and Program‐Contract Bargaining in Spanish Public Hospitals
Authors: Ventura Juan , GonzáLez Eduardo , Cárcaba Ana
Published: November 2004

Abstract This paper analyses the evolution of productivity in Spanish public hospitals during the period characterised by the use of program‐contracts. The results demonstrate that a significant improvement has occurred. The decomposition of the Malmquist productivity index shows that efficiency change has been the main contributor to productivity improvement. We also analyse the dynamic implications of program‐contract bargaining. In particular, the data support the hypothesis that the bargaining process has been subject to a ratchet effect, i.e., the more a hospital does today, the more the hospital is asked to do in the future. This result threatens the credibility of the program‐contract as an incentive system.
Low Order Approximations in Deconvolution and Regression with Errors in Variables
Authors: Carroll Raymond J. , Hall Peter
Published: November 2004

We suggest two new methods, which are applicable to both deconvolution and regression with errors in explanatory variables, for nonparametric inference. The two approaches involve kernel or orthogonal series methods. They are based on defining a low order approximation to the problem at hand, and proceed by constructing relatively accurate estimators of that quantity rather than attempting to estimate the true target functions consistently. Of course, both techniques could be employed to construct consistent estimators, but in many contexts of importance (e.g. those where the errors are Gaussian) consistency is, from a practical viewpoint, an unattainable goal. We rephrase the problem in a form where an explicit, interpretable, low order approximation is available. The information that we require about the error distribution (the error-in-variables distribution, in the case of regression) is only in the form of low order moments and so is readily obtainable by a rudimentary analysis of indirect measurements of errors, e.g. through repeated measurements. In particular, we do not need to estimate a function, such as a characteristic function, which expresses detailed properties of the error distribution. This feature of our methods, coupled with the fact that all our estimators are explicitly defined in terms of readily computable averages, means that the methods are particularly economical in computing time.
Estimation and Testing Stationarity for Double-Autoregressive Models
Authors: Ling Shiqing
Published: November 2004

The paper considers the double-autoregressive model yt = φyt−1+ɛt with ɛt =ηt√(ω+αyt−12). Consistency and asymptotic normality of the estimated parameters are proved under the condition E ln |φ +√αηt|<0, which includes the cases with |φ|=1 or |φ|>1 as well as E(εt2)=∞. It is well known that all kinds of estimators of φ in these cases are not normal when ɛt are independent and identically distributed. Our result is novel and surprising. Two tests are proposed for testing stationarity of the model and their asymptotic distributions are shown to be a function of bivariate Brownian motions. Critical values of the tests are tabulated and some simulation results are reported. An application to the US 90-day treasury bill rate series is given.
Effect of concurrent zidovudine use on the resistance pathway selected by abacavir‐containing regimens
Authors: Lanier ER , Givens N , Stone C , Griffin P , Gibb D , Walker S , Tisdale M , Irlbeck D , Underwood M , St Clair M , Ait‐Khaled M
Published: November 2004

Objectives

Abacavir (ABC) selects for four mutations (K65R, L74V, Y115F and M184V) in HIV‐1 reverse transcriptase (RT), both in vitro and during monotherapy in vivo. The aim of this analysis was to compare the selection of these and other nucleoside reverse transcriptase inhibitor (NRTI)‐associated mutations by ABC‐containing therapies in the presence and absence of concurrent lamivudine (3TC) and/or zidovudine (ZDV) and to assess the effect of these mutations on phenotypic susceptibility to the NRTIs.

Design

This study was a retrospective analysis of the patterns of NRTI‐associated mutations selected following virological failure in six multicentre trials conducted during the development of ABC.

Methods

Virological failure was defined as confirmed vRNA above 400 HIV‐1 RNA copies/mL. RT genotype and phenotype were determined using standard methods.

Results

K65R was selected infrequently by ABC‐containing regimens in the absence of ZDV (13 of 127 patients), while L74V/I was selected more frequently (51 of 127 patients). Selection of both K65R and L74V/I was significantly reduced by co‐administration of ZDV with ABC (one of 86 and two of 86 patients, respectively). Y115F was uncommon in the absence (seven of 127 patients) or presence (four of 86 patients) of ZDV. M184V was the most frequently selected mutation by ABC alone (24 of 70 patients) and by ABC plus 3TC (48 of 70 patients). Thymidine analogue mutations were associated with ZDV use. The K65R mutation conferred the broadest phenotypic cross‐resistance of the mutations studied.

Conclusions

The resistance pathway selected upon virological failure of ABC‐containing regimens is significantly altered by concurrent ZDV use, but not by concurrent 3TC use. These data may have important implications for the efficacy of subsequent lines of NRTI therapies.