Comment on Nicholas and Asghari: Pain 2006;124:269-79.
Explore the source record for details and available documents.
Adaptation, Psychological↗
Biomedical subjects
M Thompson
Publications and source records attributed to M Thompson.
Autoimmunity after islet-cell allotransplantation.
Explore the source record for details and available documents.
Autoimmunity↗
Assessment of examiner leniency and stringency ('hawk-dove effect') in the MRCP(UK) clinical examination (PACES) using multi-facet Rasch modelling.
BACKGROUND: A potential problem of clinical examinations is known as the hawk-dove problem, some examiners being more stringent and requiring a higher performance than other examiners who are more lenient. Although the problem has been known qualitatively for at least a century, we know of no previous statistical estimation of the size of the effect in a large-scale, high-stakes examination. Here we use FACETS to carry out a multi-facet Rasch modelling of the paired judgements made by examiners in the clinical examination (PACES) of MRCP(UK), where identical candidates were assessed in identical situations, allowing calculation of examiner stringency. METHODS: Data were analysed from the first nine diets of PACES, which were taken between June 2001 and March 2004 by 10,145 candidates. Each candidate was assessed by two examiners on each of seven separate tasks. with the candidates assessed by a total of 1,259 examiners, resulting in a total of 142,030 marks. Examiner demographics were described in terms of age, sex, ethnicity, and total number of candidates examined. RESULTS: FACETS suggested that about 87% of main effect variance was due to candidate differences, 1% due to station differences, and 12% due to differences between examiners in leniency-stringency. Multiple regression suggested that greater examiner stringency was associated with greater examiner experience and being from an ethnic minority. Male and female examiners showed no overall difference in stringency. Examination scores were adjusted for examiner stringency and it was shown that for the present pass mark, the outcome for 95.9% of candidates would be unchanged using adjusted marks, whereas 2.6% of candidates would have passed, even though they had failed on the basis of raw marks, and 1.5% of candidates would have failed, despite passing on the basis of raw marks. CONCLUSION: Examiners do differ in their leniency or stringency, and the effect can be estimated using Rasch modelling. The reasons for differences are not clear, but there are some demographic correlates, and the effects appear to be reliable across time. Account can be taken of differences, either by adjusting marks or, perhaps more effectively and more justifiably, by pairing high and low stringency examiners, so that raw marks can be used in the determination of pass and fail.
Adult↗
DNA-duplexes containing abasic sites: correlation between thermostability and acoustic wave properties.
Aldehydic apurinic or apyrimidinic sites that lack a nucleobase moiety are one of the most common forms of toxic lesions in DNA. In the present study, a close structural analog of such a site, the 2-(hydroxymethyl) tetrahydrofuranyl residue, was synthesized in order to act as a model for damaged nucleic acid probes. Prepared oligodeoxyribonucleotides containing one, two or three abasic sites were hybridized to complementary sequences immobilized on a gold surface using the neutravidin-biotin interaction for study by thickness shear mode acoustic wave detector. Measurement of the complex electrical impedance of an AT-cut quartz device with immobilized biotinylated nucleotide allowed the detection of changes of series resonance frequency, Deltafs, and motional resistance, Rm, associated with duplex formation. The changes as detected by the acoustic wave method correlated well with the thermostability of DNA duplexes in solution. With respect to the latter, UV-monitored melting curves indicate that both the number of sites and their localization in the double-stranded structure influence the amount by which a 19 b.p. duplex is destabilized. The presence of 3 abasic sites completely destabilized the DNA duplex.
Acoustics↗
The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes.
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.
Adolescent↗
DNA sequence-directed assembly of two peptide bioconjugates.
Peptide bioconjugates combine the molecular recognition features of the polypeptide from a DNA-binding protein and the DNA-sensitive fluorescence of an intercalating dye. Here, DNA template-directed assembly of two bioconjugate probes was examined by steady-state fluorescence resonance energy transfer and time-resolved single photon counting. The Förster critical distance was determined to be approximately 26 A for the oxazole yellow and thiazole orange donor-acceptor pair. The efficiency of energy transfer for two bioconjugates was a function of the number of intervening base pairs between two DNA cognate sites. These probes were sufficiently sensitive to detect sequence dependent curvature and polypeptide induced bending of the DNA. Molecular probes capable of examining spatial aspects of protein complexes at promoter sites could yield important information about the early events in transcription initiation.
Amino Acid Sequence↗
Modulation of store-operated Ca2+ entry by cyclic-ADP-ribose.
Store-operated Ca2+ entry plays an important role in Ca2+ homeostasis in cells but the mechanisms of control of these channels are not completely understood. We describe an investigation of the role of the CD38-cyclic-ADP-ribose (cADPR)-ryanodine-channel (RyR) signaling pathway in store-operated Ca2+ entry in human smooth muscle. We observed that human myometrial cells have a functional store-operated Ca2+ entry mechanism. Furthermore, we observed the presence of transient receptor potential 1, 3, 4, 5, and 6 ion channels in human myometrial cells. Store-operated Ca2+ transient was inhibited by at least 50-70% by several inhibitors of the RyR, including ryanodine (10 microM), dantrolene (10 microM), and ruthenium red (10 microM). Furthermore, the cell permeable inhibitor of the cADPR-system, 8-Br-cADPR (100 microM), is a potent inhibitor of the store-operated entry, decreasing the store operated entry by 80%. Pre-incubation of cells with 100 microM cADPR and the hydrolysis-resistant cADPR analog 3-deaza-cADPR (50 microM), but not with ADP-ribose (ADPR) leads to a 1.6-fold increase in the store-operated Ca2+ transient. In addition, we observed that nicotinamide (1-10 mM), an inhibitor of cADPR synthesis, also leads to inhibition of the store-operated Ca2+ transient by 50-80%. Finally, we observed that the transient receptor potential channels, RyR, and CD38 can be co-immunoprecipitated, indicating that they interact in vivo. Our observations clearly implicate the CD38-cADPR-ryanodine signaling pathway in the regulation of store-operated Ca2+ entry in human smooth muscle cells.
ADP-ribosyl Cyclase 1↗
In vivo tracking of macrophage activated killer cells to sites of metastatic ovarian carcinoma.
Radio-labelling of blood cells is an established technique for evaluating in vivo migration of normal cells to sites of pathology such as infection and haemorrhage. A limitation of cellular immunotherapies to induce anti-tumour responses is in part due to the uncertain ability of cellular effectors to reach their intended target. We extended the approach of cell radiolabelling to accurately examine the in vivo distribution of cellular immunotherapy with ex-vivo macrophage activated killer (MAK) cells. We describe the use of two methods of cell labelling for tracking the destination of autologous-derived macrophage activated killer (MAK) cells linked to the bi-specific antibody MDX-H210 delivered either by intravenous (i.v.) or intraperitoneal (i.p.) injection in ten patients with peritoneal relapse of epithelial ovarian carcinoma. Our results demonstrate the feasibility of generating high numbers and purity of GMP quality MAK cells, which can be radiolabelled with (18)F-FDG or (111)In-oxime. MAK cell administration produced minimal infusional toxicity and demonstrated a reproducible pattern of in vivo distribution and active in vivo tracking to sites of known tumour following 8 of 16 i.v. infusions or 4 of 6 i.p. infusions. However, the leakage of (18)F-FDG limited the ability to confidently confirm the tracking of MAK cells to tumour in all cases and improved PET labels are required. The addition of MDX-H210 bispecific antibody did not alter the distribution of cells to tumour sites, but did accelerate the clearance of i.v. administered MAK cells from the pulmonary circulation. This data demonstrates that cellular cancer immunotherapies may be successfully delivered to the sites of active tumour following either i.v. or i.p. injection in a proportion of patients with metastatic cancer. Incorporation of tracking studies in early cycles of cellular immunotherapy may allow selection of patients who demonstrate successful targeting of the immunotherapy for ongoing treatment.
Antibodies, Bispecific↗
An audit demonstrating a reduction in MRSA infection in a specialised vascular unit resulting from a change in infection control protocol.
INTRODUCTION: In 2003, 18% of all admissions to our vascular ward were colonised by MRSA, with an MRSA infection rate of 10.6%. Standard practice was to segregate patients with proven MRSA from the rest of the patient pool. After a prospective audit, regression analysis was used to identify factors that could stratify patients into high and low risk for MRSA colonisation. A change in isolation policy was introduced that segregated patients according to their risk of MRSA acquisition, and isolated all patients undergoing prosthetic vascular reconstruction. Antibiotic policy was also altered. This audit reports the impact of these changes on MRSA colonisation and infection rates. METHODS: The MRSA status of patients during 777 in-patient episodes was prospectively recorded during three time spans; period 1 (November 2002-April 2003) before the change in isolation and antibiotic policy and, periods 2 (August-December 2003) and 3 (October 2004-January 2005) after the change in policy. RESULTS: Hospital acquired MRSA colonisation was reduced from 10.6% in period 1, to 1.1 and 1.4% in periods 2 and 3, respectively (p<0.001). Similarly, MRSA infection rates fell from 10.6 to 2.9 and 0.9% over the same time frame (p<0.001). The most dramatic changes in MRSA infection rates occurred in patients undergoing aneurysm repair (MRSA infection 30.1% in period 1 vs. 3.9 and 2.9% in periods 2 and 3) and lower limb revascularization (31 vs. 0 vs. 4.2%). Stepwise regression analysis revealed that the system of isolation was a significant factor reducing MRSA infection and colonisation rates (p<0.001). CONCLUSIONS: These data demonstrate that a change in infection control policy can significantly reduce MRSA infection in a vascular unit.
Amoxicillin-Potassium Clavulanate Combination↗
Pseudoaneurysm after aortic coarctation repair presenting with an aortobronchial fistula successfully treated with an aortic stent graft.
Explore the source record for details and available documents.
Aneurysm, False↗
The Valiant thoracic endograft.
Thoracic aortic pathology is common, but conventional surgery carries with it a significant risk of mortality and morbidity due to thoracotomy, extensive surgical dissection, partial left lung collapse, proximal aortic cross-clamping and blood loss necessary for open thoracic aortic replacement. Endovascular techniques have the potential to remove much of this harm. However, endograft delivery to the thoracic aorta brings its own challenges; the graft and delivery system must be conformable to follow the aortic arch, flexible to track through tortuous calcified vessels, of low profile for access through the iliac arteries, and deploy accurately and with minimal force to avoid accidental side branch occlusion. The endoprosthesis must also prove to be durable. This paper reviews current indications for thoracic aortic stent grafts and the properties of an ideal endograft for deployment in the arch and descending aorta. The Medtronic Valiant TM endoprosthesis with Xcelerant TM Delivery System is a third-generation system designed specifically for the treatment of a range of thoracic aortic pathologies, including but not exclusively, aneurysms and dissections. The design of the Valiant endoprosthesis and delivery system are described in detail, and compared to the second-generation Talent system. Our early experience of using Valiant in 28 patients with a range of pathologies is described. The graft achieved an initial technical success in 93% and was easy to position and deploy. Long-term data is now required; the Virtue Registry is a prospective multicenter European registry collecting clinical and health economics data on Valiant in the management of aortic dissections.
Aortic Dissection↗
Symptom control in children and adolescents with attention-deficit/hyperactivity disorder on switching from immediate-release MPH to OROS MPH Results of a 3-week open-label study.
AIM: The aim of this study was to assess the impact of switching from immediate-release (IR) methylphenidate (MPH) to OROS MPH (CONCERTA, a once-daily long-acting MPH formulation, in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). METHODS: Subjects with ADHD aged 6-16 (n=105),who were stably maintained on their current IR MPH regimen (10-60 mg/day), were switched to 18, 36 or 54 mg OROS MPH once daily for 21 days, depending on pre-study daily MPH dose. ADHD symptoms were assessed by parents, teachers and investigators. RESULTS: By Day 21, parent/caregiver IOWA Conners ratings had decreased from baseline by 2.7 points to 5.2 (I/O), and by 1.8 points to 5.0 (O/D). Teacher IOWA Conners ratings were maintained. Decreases in IOWA Conners ratings are indicative of ADHD symptom improvement. Approximately 75% of parents and investigators rated therapy as good or excellent. OROS MPH therapy was well tolerated. CONCLUSIONS: Switching from IR MPH to OROS MPH maintained and may have improved symptom control in children and adolescents with ADHD, during the course of this study. The changes in parent/caregiver IOWA Conners ratings suggest that OROS MPH improves symptom control in the after-school period. This is consistent with the 12-h duration of action previously demonstrated for OROS MPH.
Adolescent↗
12-month efficacy and safety of OROS MPH in children and adolescents with attention-deficit/hyperactivity disorder switched from MPH.
PURPOSE: The aim of this study was to evaluate long-term clinical treatment with OROS methylphenidate (MPH) (Concerta) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) who had been previously treated with immediate release (IR) MPH. METHODS: Subjects aged 6-16 years (n=105) who were stable on IR MPH (10-60 mg/day) were switched to 18, 36 or 54 mg OROS MPH once daily for 21 days, depending on prestudy MPH dose. Subjects who benefited from OROS MPH could continue in a 12-month extension period. ADHD symptoms and treatment response were assessed by parents/caregivers and investigators. RESULTS: Out of 105 enrolled children, 101 completed the 21-day treatment phase. In all, 89 parents/caregivers (88.1%) wanted their child to continue with the study treatment into the extension phase, and 56 children (63 %) completed the 1-year trial. The parent/caregiver global assessment of satisfaction ranged from 49 to 69% during the extension phase, and 49 to 71% of investigators rated the treatment as adequate. Efficacy and satisfaction were found more commonly in patients in the older age group (10-16 years), those on a higher dose (36 mg or 54 mg) and with the predominantly inattentive ADHD subtype. OROS MPH was well tolerated. CONCLUSIONS: Children and adolescents can effectively and safely be switched from IR MPH to OROS MPH with improved symptom control and compliance.
Adolescent↗
Pantoprazole in severe acid-peptic disease: the effectiveness and safety of 5 years' continuous treatment.
OBJECTIVE: This is our final report on the clinical effectiveness and safety of long-term pantoprazole in patients with severe peptic ulcer or reflux disease during continuous treatment for up to 5 years. METHODS: Patients (n= 150) with peptic ulcer or reflux erosive oesophagitis running an aggressive course or with complications, and refractory to H2-receptor antagonists, were entered into this 5-year programme. Assessment was by serial endoscopy, clinical examination, serum gastrin estimation, gastric mucosal histology and mucosal endocrine cell quantification. RESULTS: Healing results were presented earlier. The estimated rates of remission on maintenance treatment with pantoprazole (n = 115) were 82% at 1 year, 75% at 2 years, 72% at 3 years, 70% at 4 years and 68% at 5 years. Helicobacter pylori infection appeared not to influence the outcome in reflux patients, with roughly two-thirds continuing in remission irrespective of infection. Only four patients had adverse events considered to be definitely related to pantoprazole. Median gastrin levels rose by 1.5-2-fold and were higher in those with H. pylori infection; 13 patients had levels >500 ng/L on at least one occasion, but these high levels were not sustained. Histological changes were more marked in patients infected with H. pylori: chronic gastritis decreased in the antrum and increased in the corpus, which also showed atrophic changes. The total number of endocrine cells in the antrum showed little variation over 60 months but fell by around one-third in the corpus. CONCLUSION: Long-term treatment with pantoprazole is effective and safe.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Patch corrugation on duplex ultrasonography may be an early warning of prosthetic patch infection.
Four of 10 patients presenting with prosthetic patch infection after carotid endarterectomy (CEA) were noted to have Duplex evidence of 'corrugation' of the prosthetic patch, without false aneurysm formation. In three, corrugation preceded diagnosis of overt patch infection by up to 11 months. In the fourth patient, awareness of the potential significance of patch corrugation enabled timely treatment of an otherwise unrecognized patch infection. Even if other imaging modalities are normal, the presence of patch corrugation on Duplex should prompt the surgeon to (at least) consider the possibility of patch infection.
Aged↗
Systemic scleroderma: a spatiotemporal clustering.
BACKGROUND AND AIMS: The aetiology of systemic scleroderma remains poorly understood. Twin studies suggest a low genetic input. Of the incriminated environmental agents, silica and vinyl chloride monomer exposure appear the most convincing. Spatiotemporal clustering has been demonstrated only three times previously. We now report a fourth cluster around Edenhope, western Victoria in terms of numerator and denominator estimates, cumulative incidence, distribution in time and space, and possible aetiological factors. METHODS: Prevalence/cumulative incidence numerator and denominator values were obtained and validated. Each case was age-and gender-matched with two controls. A standardized postal questionnaire was used to obtain data on current, past history, family history, and occupational and non-occupational environmental exposure. RESULTS: Six systemic scleroderma cases and one mixed connective tissue disease patient with a predominance of scleroderma features were identified. The 5-year cumulative incidence was 6.1/10,000, tenfold higher than the Sydney estimates for a similar, though non-identical time period. The gender ratio was 1:1. No cases were genetically related. A family history of scleroderma was validated in one instance and a family history of Raynaud's was noted in first degree relatives of two cases and one control. In all instances, Edenhope residence preceded disease onset. No one environmental agent was implicated in all cases. CONCLUSION: A spatiotemporal cluster of systemic scleroderma was confirmed and validated. It occurred with a tenfold increased cumulative incidence to that expected and also extended beyond the initially defined 50 km radius of Edenhope. The cases identified were not related. Although no one specific environmental agent was identified, the spatiotemporal clustering would be compatible with an agent occurring at relatively high frequency, but with low disease conversion rates, such as silica inhalation (assuming sufficiently small particle size) or reaction to an infective agent.
Aged↗
Thiamine deficiency in dogs due to the feeding of sulphite preserved meat.
A 6-year-old dog, a 4-year-old dog and three 7-week-old puppies were diagnosed with thiamine deficiency caused by feeding sulphite treated meat. The 6-year-old dog presented with a history of inappetence, weight loss and vomiting that rapidly progressed to signs of multifocal intracranial disease including mental dullness, paresis, seizures, spontaneous nystagmus and strabismus. Thiamine pyrophosphate effect was elevated at 58% and magnetic resonance imaging revealed bilaterally symmetrical hyperintensity of the caudate nucleus and rostral colliculi. The dog recovered with thiamine supplementation. The 4-year-old dog and three 7-week-old puppies also presented with rapidly progressive multifocal central nervous system signs including ataxia, paresis, increased muscle tone, seizures, nystagmus and exophthalmos. The 4-year-old dog made a rapid recovery with thiamine supplementation. Euthanasia and necropsy of a puppy revealed malacia of multiple brainstem nuclei and oedema of the cerebral cortex. These findings were consistent with thiamine deficiency.
Animal Feed↗