GPi deep brain stimulation for Tourette syndrome improves tics and psychiatric comorbidities.
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Adolescent↗
Biomedical subjects
R Simpson
Publications and source records attributed to R Simpson.
Coherent combination of high-power, zigzag slab lasers.
We demonstrate a scalable architecture for a high-power, high-brightness, solid-state laser based on coherent combinations of master oscillator power amplifier chains. A common master oscillator injects a sequence of multikilowatt Nd:YAG zigzag slab amplifiers. Adaptive optics correct the wavefront of each amplified beamlet. The beamlets are tiled side by side and actively phase locked to form a single output beam. The laser produces 19 kW with beam quality <2x diffraction limited. To the best of our knowledge, this is the brightest cw solid-state laser demonstrated to date.
Journal Article↗
Maternal exposure to low levels of ambient air pollution and preterm birth in Brisbane, Australia.
BACKGROUND: [corrected] There is evidence that maternal exposure to ambient air pollution during pregnancy is associated with adverse birth outcomes. OBJECTIVE: To assess preterm birth (PTB) in relation to maternal exposure to ambient air pollution. DESIGN: Retrospective cohort. SETTING: Brisbane, Australia. POPULATION: A total of 28,200 singleton live births for the period of 1 July 2000 to 30 June 2003. METHODS: Average maternal exposure estimates for ambient particulate matter (PM(10) and bsp), ozone (O(3)) and nitrogen dioxide were calculated over the first 3 months after last menstrual period (LMP) and the last 3 months prior to birth (individually and combined as trimesters). MAIN OUTCOME MEASURES: PTB was defined as gestation <37 weeks and odds ratios (OR) were calculated for PTB per interquartile range increase in the maternal exposure estimate for each pollutant. Various covariates were controlled for, including season of birth. RESULTS: Exposure to PM(10) and O(3) during trimester one was associated with an increased risk of PTB (OR = 1.15, 95% CI 1.06-1.25 and OR = 1.26, 95% CI 1.10-1.45, respectively). The PM(10) exposure effect associated with trimester one was strongly related to exposure during the first month post-LMP (PM(10), month one; OR = 1.19, 95% CI 1.13-1.26). CONCLUSION: These results suggest that maternal exposure to low levels of ambient air pollution is associated with PTB.
Air Pollutants↗
[Thiamine retention as a function of thermal processing conditions: canned salmon].
The present work studied the effect of different treatments at high temperatures on the nutritional properties of thiamine retention and color measurement experimentally. Canned salmon (Salmo salar) was processed under different temperatures and time conditions (110 degrees C for 135 minutes; 114 degrees C for 89 minutes; 118 degrees C for 69 minutes and 121 degrees C for 62 minutes). Thiamine was determined by HPLC before and after the process. Color changes, due to processing conditions, were also measured utilizing a Hunter colorimeter. The canning was prepared in 300 x 407 cans and sterilized until Fo value reached 6 min. The nutritional value or index represented by the B1 vitamin or thiamine was affected by high temperature and time exposition. The lowest loss of thiamine of 19.2% was obtained in the canned salmon sterilized at 114 degrees C for 89 minutes. The color in canned salmon was different from the raw material, with a severe loss of red color and a greater clarity of the meat.
Animals↗
The effects of pre-weaning undernutrition on the expression levels of free radical deactivating enzymes in the mouse brain.
A mild degree of undernutrition brought about by restricting the amount of food in the diet is known to alter the life span of an animal. It has been hypothesised that this may be related to the effects of undernutrition on an animals anti-oxidant defense system. We have therefore, used real-time PCR (rt-PCR) techniques to determine the levels of mRNA expression for manganese superoxide dismutase (MnSOD), copper/zinc superoxide dismutase (Cu/ZnSOD), glutathione peroxidase 1 (GPx 1) and catalase in the brains of Quackenbush mice undernourished from conception until 21-post-natal days of age. It was found that 21- and 61-day-old undernourished mice had a deficit in the expression of Cu/ZnSOD in both the cerebellum and forebrain regions compared to age-matched controls. The expression of MnSOD was found to be greater in the cerebellum, but not the forebrain region, of 21-day-old undernourished mice. There were no significant differences in the expression of GPx 1 and catalase between control and undernourished or previously undernourished mice. Our results confirm that undernutrition during the early life of a mouse may disrupt some of the enzymes involved in the anti-oxidant defense systems.
Brain↗
Improving access to diagnostics: an evaluation of a satellite laboratory service in the emergency department.
OBJECTIVES: To measure the impact of a satellite laboratory upon laboratory result turnaround times and clinical decision making times. DESIGN: A prospective cohort study, the intervention group had blood tests sent Monday to Friday 12 noon to 8 pm and the control group had blood tests sent outside these hours. The data were collected over a six week period before the laboratory was opened, and a subsequent six week period. SETTING: An urban teaching hospital emergency department. PARTICIPANTS: 1065 patients requiring blood tests. MAIN OUTCOME MEASURE: Time from the blood sample being sent to the laboratory to the results being available on the clinician's computer. RESULTS: The time to haematology (blood count) results in the intervention group decreased by 47.2 minutes (95% CI 38.3 to 56.1, p<0.001) after the laboratory was opened. The corresponding control group times were unchanged (0.6 minutes; -13.8 to 15.0, p = 0.94). Similar sized differences were also seen for haemostasis (d-dimer) testing 66.1 (41.8 to 90.4) minutes compared with -14.2 (-47.1 to 18.7) and chemistry 41.3 (30.3 to 52.2) compared with -4.2 (-17.4 to 8.9) testing. Decisions to discharge patients were significantly faster (28.2 minutes, 13.5 to 42.8, p<0.0001) in the intervention group after the laboratory was opened (controls; -2.6 minutes -27.0 to 21.7). No change was seen with decisions to admit patients. There was a trend for earlier laboratory results modifying intravenous drug or fluids orders, or both (p = 0.06) CONCLUSION: A comprehensive satellite laboratory service is an important adjunct to improve the timeliness of care in the emergency department.
Decision Making↗
Sinonasal tubulopapillary low-grade adenocarcinoma. Histopathological, immunohistochemical and ultrastructural features of poorly recognised entity.
We present the clinicopathological, histological and immunohistochemical findings of six cases of primary tubulopapillary low-grade adenocarcinoma of the sinonasal tract with ultrastructural examination in one case. Due to its unique features, we believe that primary tubulopapillary low-grade adenocarcinoma of the sinonasal tract represents a tumour entity different from any tumours generally recognised in the sinonasal region. Our cases had an equal sex incidence, with an age range of 44-76 years. The tumour has a tendency to recur, but none of our six patients developed metastases. We feel that it is important to separate this tumour entity from other types of sinonasal adenocarcinomas that exhibit a papillary growth pattern, as they frequently pursue a much more aggressive clinical course than the tumours in this study.
Adenocarcinoma↗
Infantile viral gastroenteritis: on the way to closing the diagnostic gap.
A total of 305 faecal specimens collected from children under the age of 5 who presented with symptoms of acute gastroenteritis either as inpatients at Addenbrooke's Hospital (N = 100) or to General Practitioners in East Anglia (N = 205) during 1999-2001 were tested for the presence of rotavirus, norovirus, sapovirus, enteric adenoviruses (Group F, serotypes 40 and 41), and astrovirus. An aetiologic agent was found in 184 specimens (60.3%). The most commonly found single viral pathogen was rotavirus (27.9%), followed by norovirus (13.4%), enteric adenoviruses (7.9%), astrovirus (2.3%), and sapovirus (1%). Mixed infections were observed in 27 specimens (8.9%), and no aetiologic agent was found in over a third of the specimens tested. These data demonstrate that the diagnostic gap can be reduced considerably through the use of molecular amplification and detection techniques. However, additional work is required to reduce this deficit further by optimising sampling algorithms and by identifying other agents associated with viral gastroenteritis.
Adenoviruses, Human↗
NSAIDs: the emperor's new dogma?
The spectacular marketing success of the selective cyclooxygenase 2 (COX-2) inhibitors is largely based on efficacy comparable with conventional non-steroidal anti-inflammatory drugs (NSAIDs) with vastly improved gastrointestinal safety. The additional key to the marketing success is the purity and simplicity of the message-that is, COX-1 inhibition causes the gastrointestinal side effects of NSAIDs (COX-1 dogma) while COX-2 blocking confers the therapeutic benefits (COX-2 dogma). Adherence to the COX dogmas with development of COX-2 selective agents has undoubtedly benefited many patients, but ironically their scientific basis is now seriously challenged by experimentation.
Animals↗
COX-1, COX-2 and the topical effect in NSAID-induced enteropathy.
The side effects of NSAIDs are equally evident in the stomach and the small bowel. The latter is increasingly seen as being clinically significant, contributing substantially to the iron-deficiency anaemia that is so common in patients with rheumatoid arthritis. Furthermore, NSAID-enteropathy may be associated with life-threatening events. The pathogenesis of NSAID-enteropathy is uncertain but inhibition of COX-1 is believed to be of pivotal importance. However there is increasing evidence that COX-2 inhibition and the topical effect may have a synergistic detrimental action. We examined the role of COX-1, COX-2 and the so called topical effect of acidic NSAIDs. We found that COX-1 or COX-2 inhibition and the topical effect alone do not damage the GI tract. Dual inhibition of COX-1 and COX-2 results in intestinal inflammation similar to that caused by Indomethacin. The topical effect may act synergistically in this damage. The conventional view that the mechanism of gastrointestinal damage is principally caused by COX-1 inhibition needs to be revised in view of recent studies using selective inhibitors of the COX enzymes and COX knockout animals.
Journal Article↗
2, 4-diamino-6- hydroxy pyrimidine inhibits NSAIDs induced nitrosyl-complex EPR signals and ulcer in rat jejunum.
BACKGROUND: It has been suggested that one aspect of non-steroidal anti-inflammatory drugs induced intestinal damage is due to either uncoupling of mitochondrial oxidative phosphorylation or inhibition of electron transport. We investigated the latter possibility using electron paramagnetic resonance spectroscopy. RESULTS: Electron paramagnetic studies of NSAIDS on sub-mitochondrial particles revealed that indomethacin, but not with nabumetone, bound to a site near to Complex I and ubiquinone to generate a radical species. Normal rats exhibited prominent [3Fe-4S]ox signals (g approximately 2.01) at 20 K. One hour after indomethacin there was a prominent, intense and broad absorption pattern at (g approximately 2.07) suggesting, appearance of radical species overlapping [3Fe-4S]ox and was unaffected by pretreatment with 2,4 diamino -6-hydroxy pyrimidine. At 24 hrs, when macroscopic ulcers were seen, there was a new signal due to a nitric oxide radical (NO*). In contrast, nabumetone and 2,4 diamino-6-hydroxy pyrimidine pre-treated animals receiving indomethacin exhibited electron paramagnetic resonance spectra identical to those of controls at 24 hrs and neither was associated with small intestinal ulcers. Indomethacin and 2,4 diamino hydroxy pyrimidine pre-treated rats, but not nabumetone, had increased intestinal permeability. CONCLUSION: The results suggest that the in vivo effects of indomethacin modulate the mitochondrial respiratory chain directly at 1 h and 24 h through formation of nitric oxide. NO* appears to play an important role in the late pathogenic stages of NSAID enteropathy and may be the site for targeted treatment to reduce their toxicity.
Animals↗
Identification of two topologically independent domains in RAG1 and their role in macromolecular interactions relevant to V(D)J recombination.
V(D)J recombination is instigated by the recombination-activating proteins RAG1 and RAG2, which catalyze site-specific DNA cleavage at the border of the recombination signal sequence (RSS). Although both proteins are required for activity, core RAG1 (the catalytically active region containing residues 384-1008 of 1040) alone displays binding specificity for the conserved heptamer and nonamer sequences of the RSS. The nonamer-binding region lies near the N terminus of core RAG1, whereas the heptamer-binding region has not been identified. Here, potential domains within core RAG1 were identified using limited proteolysis studies. An iterative procedure of DNA cloning, protein expression, and characterization revealed the presence of two topologically independent domains within core RAG1, referred to as the central domain (residues 528-760) and the C-terminal domain (residues 761-980). The domains do not include the nonamer-binding region but rather largely span the remaining relatively uncharacterized region of core RAG1. Characterization of macromolecular interactions revealed that the central domain bound to the RSS with specificity for the heptamer and contained the predominant binding site for RAG2. The C-terminal domain bound DNA cooperatively but did not show specificity for either conserved RSS element. This domain was also found to self-associate, implicating it as a dimerization domain within RAG1.
Animals↗
Rehabilitation that works--vocational outcomes following rehabilitation for occupational musculoskeletal pain.
AIMS: To describe the short term vocational outcome for accident compensation claimaints with disabling musculoskeletal pain following a comprehensive, interdisciplinary rehabilitation programme. METHODS: A telephone follow-up audit of clients who had undertaken a rehabilitation programme characterised by a cognitive-behavioural approach with self-management, reconditioning, vocational rehabilitation and psychological pain management. RESULTS: Of 62 clients who had undergone a rehabilitation programme, we obtained follow-up information on 49 (79%). These were predominantly male, aged in their mid 30s, manual workers with low back pain and a median sick leave of twelve months. At a median of five months a vocational success was achieved in 75%: working full time (47%), part time (12%) or actively looking for work (16%). Of those in work, 48% went back to the same job, 7% went back to the same job but with a different employer and 15% went to a different job that used the same skills. Logistic regression analysis showed that duration of work disability was the major predictor of vocational success (OR 0.36, 95% CI 0.18 to 0.78, for a difference of twelve months). CONCLUSION: Despite the uncontrolled nature of these results, it is likely that the rehabilitation programme had a significant impact in getting compensation claimants back to work. Only a minority require substantive retraining and early intervention is associated with a better outcome.
Adult↗
High-throughput, semi-automated determination of a cyclooxygenase II inhibitor in human plasma and urine using solid-phase extraction in the 96-well format and high-performance liquid chromatography with post-column photochemical derivatization-fluorescence detection.
Compound I, 5-chloro-3-(4-methanesulfonylphenyl)-6'-methyl-[2,3']bipyridinyl, has been found to be a specific inhibitor of the enzyme cyclooxygenase II (COX II). The anti-inflammatory properties of this compound are currently being investigated. HPLC assays for the determination of this analyte in human plasma and human urine have been developed. Isolation of I and the internal standard (II) was achieved by solid-phase extraction (SPE) in the 96-well format. A C8 SPE plate was used for the extraction of the drug from human plasma (recovery >90%) while a mixed-mode (C8/Cation) SPE plate was used to isolate the analytes from human urine (recovery approximately 71%). The analyte and internal standard were chromatographed on a Keystone Scientific Prism-RP guard column (20 x 4.6 mm) connected to a Prism-RP analytical column (150 x 4.6 mm), using a mobile phase consisting of 45% acetonitrile in 10 mM acetate buffer (pH = 4); the analytes eluted at retention times of 5.2 and 6.9 min for I and II, respectively. Compounds I and II were found to form highly fluorescent products after exposure to UV light (254 nm). Thus, the analytes were detected by fluorescence (lambda(ex) = 260 nm, lambda(em) =375 nm) following post-column photochemical derivatization. Eight point calibration curves over the concentration range of 5-500 ng/ml for human plasma and human urine yielded a linear response (R2>0.99) when a 1/y weighted linear regression model was employed. Based on the replicate analyses (n = 5) of spiked standards, the within-day precision for both assays was better than 7% C.V. at all points on the calibration curve; within-day accuracy was within 5% of nominal at all standard concentrations. The between-run precision and accuracy of the assays, as calculated from the results of the analysis of quality control samples, was better than 8% C.V. and within 8% of nominal. I was found to be stable in human plasma and urine for at least 8 and 2 months, respectively. In addition, the human plasma assay was semi-automated in order to improve sample throughput by utilizing a Packard liquid handling system and a Tom-Tec Quadra 96 SPE system. The precision and accuracy of the semi-automated procedure were comparable to the manual procedure. Over 5000 clinical samples have been analyzed successfully using these methods.
Automation↗
Rapid response to radiation of choroidal melanoma.
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Brachytherapy↗
Baby massage classes and the work of the International Association of Infant Massage.
This article describes the role of the International Association of Infant Massage (IAIM) in promoting the importance of touch for the developing relationship between the parents and infants. Infants are unique personalities and it is important that the parent learns how to respond appropriately to the infant's needs. Infant massage classes can demonstrate and promote interaction with infants using eye-to-eye contact, recognizing infant cues, talking and singing, and responding in a loving and sensitive manner. The photographs are of an infant massage class held recently in Leicestershire.
Child Health Services↗
Preretinal neovascularisation associated with choroidal melanoma.
BACKGROUND: The rare occurrence of iris neovascularisation and choroidal (subretinal) neovascularisation in patients with choroidal melanoma has been reported. However, the occurrence of preretinal neovascularisation (NVE) fed from the retinal circulation in eyes with choroidal melanoma is far less frequently reported. METHODS: Three case reports of choroidal melanoma with the very rare finding of overlying NVE. RESULTS: The three patients had choroidal melanomas, localised serous retinal detachment, and NVE. Two cases showed definite retinal capillary non-perfusion, and one of these two cases demonstrated retinal telangiectasis. One patient's melanoma responded quickly to iodine-125 plaque radiotherapy; however, the retinal neovascularisation persisted and caused vitreous haemorrhage. Localised scatter photocoagulation was successful in causing the complete regression of the neovascularisation. The other two patients had their eyes enucleated (one with planned pre-enucleation external beam radiotherapy). Demonstration of preretinal vessels in one of the cases was possible in histological sections. CONCLUSION: Preretinal neovascularisation may occur as a complication of choroidal melanoma. Possible aetiologies include the release of tumour angiogenic factors, inflammation, chronic retinal detachment with secondary retinal ischaemia, retinal vascular occlusion secondary to retinal vessel invasion by the tumour, or following radiation therapy. Optimal management of the neovascularisation is not known at this time. Supplemental localised scatter photocoagulation may be of benefit in some cases.
Adult↗
The public awareness of aphasia: an international survey.
We surveyed 929 shoppers in Exeter (England), Louisiana (USA) and Sydney (Australia) to determine what they knew of aphasia. Between 10% and 18% said they had heard of aphasia but only between 1.5% and 7.6% had even some basic knowledge of aphasia. We found that more females knew something about aphasia than males and that older people were more likely to have heard of it, although those with some knowledge were significantly younger. Informants had heard of aphasia mainly through their work or the media and were mainly professionals like teachers, nurses, therapists, managers and administrators, followed by a retired/student group. We found some differences in awareness levels in the different locations we sampled. Results have implications for targeting awareness raising and campaigning.
Adolescent↗