Publications
221 results found
Kumar S, Dunsby C, De Beule PAA, et al., 2007, Multifocal multiphoton excitation and time correlated single photon counting detection for 3-D fluorescence lifetime imaging, Optics Express, Vol: 15, Pages: 12548-12561
We report a multifocal multiphoton time-correlated single photon counting (TCSPC) fluorescence lifetime imaging (FLIM) microscope system that uses a 16 channel multi-anode PMT detector. Multiphoton excitation minimizes out-of-focus photobleaching, multifocal excitation reduces non-linear in-plane photobleaching effects and TCSPC electronics provide photon-efficient detection of the fluorescence decay profile. TCSPC detection is less prone to bleaching- and movementinduced artefacts compared to wide-field time-gated or frequency-domain FLIM. This microscope is therefore capable of acquiring 3-D FLIM images at significantly increased speeds compared to single beam multiphoton microscopy and we demonstrate this with live cells expressing a GFP tagged protein. We also apply this system to time-lapse FLIM of NAD(P)H autofluorescence in single live cells and report measurements on the change in the fluorescence decay profile following the application of a known metabolic inhibitor.
Roberts K, Facer P, Shenoy R, et al., 2007, Use of skin biopsy and contact heat evoked potentials to identify possible small fibre variants of inflammatory neuropathy and Guillain-Barre syndrome, ABN Spring Scientific Meeting 2007, Publisher: B M J PUBLISHING GROUP, Pages: 1025-1025, ISSN: 0022-3050
O'Hanlon S, Facer P, Simpson KD, et al., 2007, Neuronal markers in allergic rhinitis: Expression and correlation with sensory testing, LARYNGOSCOPE, Vol: 117, Pages: 1519-1527, ISSN: 0023-852X
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- Citations: 45
Yilmaz Z, Renton T, Yiangou Y, et al., 2007, Burning mouth syndrome as a trigeminal small fibre neuropathy: Increased heat and capsaicin. receptor TRPV1 in nerve fibres correlates with pain score, JOURNAL OF CLINICAL NEUROSCIENCE, Vol: 14, Pages: 864-871, ISSN: 0967-5868
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- Citations: 176
Atherton DD, Facer P, Roberts KM, et al., 2007, Use of the novel contact heat evoked potential stimulator (CHEPS) for the assessment of small fibre neuropathy: correlations with skin flare responses and intra-epidermal nerve fibre counts, BMC Neurology, Vol: 7, ISSN: 1471-2377
BackgroundThe Contact Heat Evoked Potential Stimulator (CHEPS) rapidly stimulates cutaneous small nerve fibres, and resulting evoked potentials can be recorded from the scalp. We have studied patients with symptoms of sensory neuropathy and controls using CHEPS, and validated the findings using other objective measures of small nerve fibres i.e. the histamine-induced skin flare response and intra-epidermal fibres (IEF), and also quantitative sensory testing (QST), a subjective measure.MethodsIn patients with symptoms of sensory neuropathy (n = 41) and healthy controls (n = 9) we performed clinical examination, QST (monofilament, vibration and thermal perception thresholds), nerve conduction studies, histamine-induced skin flares and CHEPS. Skin punch biopsies were immunostained using standard ABC immunoperoxidase for the nerve marker PGP 9.5 or the heat and capsaicin receptor TRPV1. Immunoreactive IEF were counted per length of tissue section and epidermal thickness recorded.ResultsAmplitudes of Aδ evoked potentials (μV) following face, arm or leg stimulation were reduced in patients (e.g. for the leg: mean ± SEM – controls 11.7 ± 1.95, patients 3.63 ± 0.85, p = 0.0032). Patients showed reduced leg skin flare responses, which correlated with Aδ amplitudes (rs = 0.40, p = 0.010). In patient leg skin biopsies, PGP 9.5- and TRPV1-immunoreactive IEF were reduced and correlated with Aδ amplitudes (PGP 9.5, rs = 0.51, p = 0.0006; TRPV1, rs = 0.48, p = 0.0012).ConclusionCHEPS appears a sensitive measure, with abnormalities observed in some symptomatic patients who did not have significant IEF loss and/or QST abnormalities. Some of the latter patients may have early small fibre dysfunction or ion channelopathy. CHEPS provides a clinically practical, non-invasive and objective measure, and can be a useful additional tool for the assessment of sensory small fibre neuropathy. Although further evaluation is required, the technique
Anand P, Atherton D, Facer P, et al., 2007, Use of the novel contact heat evoked potential stimulator for the diagnosis of small fibre neuropathies: Correlations with skin flare and intra-epidermal nerve fibre counts, Annual Meeting of the Peripheral-Nerve-Society, Publisher: BLACKWELL PUBLISHING, Pages: 3-4, ISSN: 1085-9489
Facer P, Casula MA, Smith GD, et al., 2007, Differential expression of the capsaicin receptor TRPV1 and related novel receptors TRPV3, TRPV4 and TRPM8 in normal human tissues and changes in traumatic and diabetic neuropathy, BMC Neurology, Vol: 7, ISSN: 1471-2377
BackgroundTransient receptor potential (TRP) receptors expressed by primary sensory neurons mediate thermosensitivity, and may play a role in sensory pathophysiology. We previously reported that human dorsal root ganglion (DRG) sensory neurons co-expressed TRPV1 and TRPV3, and that these were increased in injured human DRG. Related receptors TRPV4, activated by warmth and eicosanoids, and TRPM8, activated by cool and menthol, have been characterised in pre-clinical models. However, the role of TRPs in common clinical sensory neuropathies needs to be established.MethodsWe have studied TRPV1, TRPV3, TRPV4, and TRPM8 in nerves (n = 14) and skin from patients with nerve injury, avulsed dorsal root ganglia (DRG) (n = 11), injured spinal nerve roots (n = 9), diabetic neuropathy skin (n = 8), non-diabetic neuropathic nerve biopsies (n = 6), their respective control tissues, and human post mortem spinal cord, using immunohistological methods.ResultsTRPV1 and TRPV3 were significantly increased in injured brachial plexus nerves, and TRPV1 in hypersensitive skin after nerve repair, whilst TRPV4 was unchanged. TRPM8 was detected in a few medium diameter DRG neurons, and was unchanged in DRG after avulsion injury, but was reduced in axons and myelin in injured nerves. In diabetic neuropathy skin, TRPV1 expressing sub- and intra-epidermal fibres were decreased, as was expression in surviving fibres. TRPV1 was also decreased in non-diabetic neuropathic nerves. Immunoreactivity for TRPV3 was detected in basal keratinocytes, with a significant decrease of TRPV3 in diabetic skin. TRPV1-immunoreactive nerves were present in injured dorsal spinal roots and dorsal horn of control spinal cord, but not in ventral roots, while TRPV3 and TRPV4 were detected in spinal cord motor neurons.ConclusionThe accumulation of TRPV1 and TRPV3 in peripheral nerves after injury, in spared axons, matches our previously reported changes in avulsed DRG. Reduction of TRPV1 levels in nerve fibres in diabetic
De Beule P, Owen DM, Manning HB, et al., 2007, Rapid hyperspectral fluorescence lifetime imaging, MICROSCOPY RESEARCH AND TECHNIQUE, Vol: 70, Pages: 481-484, ISSN: 1059-910X
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- Citations: 44
Htut M, Misra VP, Anand P, et al., 2007, Motor recovery and the breathing arm after brachial plexus surgical repairs, including re-implantation of avulsed spinal roots into the spinal cord, JOURNAL OF HAND SURGERY-BRITISH AND EUROPEAN VOLUME, Vol: 32E, Pages: 170-178, ISSN: 0266-7681
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- Citations: 37
Akbar A, Yiangou Y, Facer P, et al., 2007, Increased trpv1 expressing nerve fibres in colonic biopsies from irritable bowel syndrome patients correlate with the degree of abdominal pain, Annual Meeting of the British-Society-of-Gastroenterology, Publisher: B M J PUBLISHING GROUP, Pages: A19-A19, ISSN: 0017-5749
Mukerji G, Waters J, Agarwal SK, et al., 2007, Bladder cooling reflex distinguishes detrusor overactivity disorders from painful bladder syndrome, Fall Meeting of the Association-of-British-Neurologists, Publisher: B M J PUBLISHING GROUP, Pages: 213-213, ISSN: 0022-3050
Roberts KM, Atherton DD, Facer P, et al., 2007, Increase in cerebral heat evoked potential parallels burning pain triggered by exercise in a patient with small nerve fibre dysfunction, Fall Meeting of the Association-of-British-Neurologists, Publisher: B M J PUBLISHING GROUP, Pages: 219-219, ISSN: 0022-3050
Yiangou Y, Yilmaz Z, Renton T, et al., 2007, Burning mouth syndrome as a trigeminal small fibre neuropathy: Increased heat and capsaicin receptor TRPV1 in spared nerve fibres correlates with pain score, Fall Meeting of the Association-of-British-Neurologists, Publisher: B M J PUBLISHING GROUP, Pages: 218-219, ISSN: 0022-3050
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- Citations: 1
Sanchez D, Arand U, Gorelik J, et al., 2007, Localized and non-contact mechanical stimulation of dorsal root ganglion sensory neurons using scanning ion conductance microscopy, JOURNAL OF NEUROSCIENCE METHODS, Vol: 159, Pages: 26-34, ISSN: 0165-0270
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- Citations: 37
Korchev Y, Sanchez D, Anand P, et al., 2007, "Non-contact" mechanical characterization and stimulation of cells using scanning ion conductance microscopy., 51st Annual Meeting of the Biophysical-Society, Publisher: BIOPHYSICAL SOCIETY, Pages: 33A-33A, ISSN: 0006-3495
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- Citations: 1
Anand P, Aziz Q, Willert R, et al., 2007, Peripheral and central mechanisms of visceral sensitization in man, NEUROGASTROENTEROLOGY AND MOTILITY, Vol: 19, Pages: 29-46, ISSN: 1350-1925
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- Citations: 134
De Beule PAA, Dunsby C, Owen DM, et al., 2007, A novel hyperspectral lifetime probe for autofluorescence - art. no. 643303, Conference on Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications VII, Pages: 43303-43303
The application of autofluorescence in non-invasive medical diagnostics could have great potential. Two major drawbacks inherent to this approach are low signal levels compared to those from exogenous fluorescent probes and complexity caused by the multiplicity of fluorescent biomolecules in tissue. Here we present a new optical system that is based on single channel detection via all optical fiber and call measure the fluorescence emission spectrum and fluorescence lifetime simultaneously for excitation wavelengths of 355 and 435nm. Single channel measurements integrate the signal normally available in all imaging setup and therefore have a better signal-to-noise ratio. Resolving both the fluorescence emission spectrum and fluorescence lifetime provides the opportunity to discriminate multiple fluorophores. This instrument is intended for NAD(P)H and flavin measurements for the dynamic monitoring of cellular metabolism and optical measurements of cancerous tissue. Initial results from a study of live cells and a clinical study of human skin lesions are presented.
Owen DM, Manning HB, de Beule P, et al., 2007, Development of a hyperspectral fluorescence lifetime imaging microscope and its application to tissue imaging, Conference on Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues V, Publisher: SPIE-INT SOC OPTICAL ENGINEERING, ISSN: 0277-786X
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- Citations: 2
Owen D M, Manning H B, de Beule P, et al., 2007, Rapid hyperspectral fluorescence lifetime imaging, IMAGING, MANIPULATION AND ANALYSIS OF BIOMOLECULES, CELLS, AND TISSUES V, BIOS, Publisher: SPIE
Mukerji G, Waters J, Chessell IP, et al., 2006, Pain during ice water test distinguishes clinical bladder hypersensitivity from overactivity disorders., BMC Urology, Vol: 6, ISSN: 1471-2490
BACKGROUND: The Bladder cooling reflex (BCR) i.e. uninhibited detrusor contractions evoked by intravesical instillation of cold saline, is a segmental reflex believed to be triggered by menthol sensitive cold receptors in the bladder wall, with the afferent signals transmitted by C fibres. The BCR is a neonatal reflex that becomes suppressed by descending signals from higher centres at approximately the time when the child gains full voluntary control of voiding. It re-emerges in adults with neurogenic detrusor overactivity as a consequence of loss of central descending inhibition, resulting from conditions such as spinal cord injury or multiple sclerosis. We have recently shown an increase of nerve fibres expressing the cool and menthol receptor TRPM8 in both overactive (IDO) and painful bladder syndrome (PBS), but its functional significance is unknown. We have therefore studied the bladder cooling reflex and associated sensory symptoms in patients with PBS and overactivity disorders. METHODS: The BCR, elicited by ice water test (IWT) was performed in patients with painful bladder syndrome (PBS, n = 17), idiopathic detrusor overactivity (IDO, n = 22), neurogenic detrusor overactivity (NDO, n = 4) and stress urinary incontinence (as controls, n = 21). The IWT was performed by intravesical instillation of cold saline (0 - 4 degrees C). A positive IWT was defined as presence of uninhibited detrusor contraction evoked by cold saline, associated with urgency or with fluid expulsion. Patients were asked to report and rate any pain and cold sensation during the test. RESULTS: A positive IWT was observed in IDO (6/22, 27.3%) and NDO (4/4, 100%) patients, but was negative in all control and PBS patients. Thirteen (76.5%) PBS patients reported pain during the IWT, with significantly higher pain scores during ice water instillation compared to the baseline (P = 0.0002), or equivalent amount of bladder filling (100 mls) with saline at room temperature (P = 0.015). None of the
Atherton DD, Taherzadeh O, Facer P, et al., 2006, The potential role of nerve growth factor (NGF) in painful neuromas and the mechanism of pain relief by their relocation to muscle, JOURNAL OF HAND SURGERY-BRITISH AND EUROPEAN VOLUME, Vol: 31B, Pages: 652-656, ISSN: 0266-7681
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- Citations: 38
Htut M, Misra P, Anand P, et al., 2006, Pain phenomena and sensory recovery following brachial plexus avulsion injury and surgical repairs, JOURNAL OF HAND SURGERY-BRITISH AND EUROPEAN VOLUME, Vol: 31B, Pages: 596-605, ISSN: 0266-7681
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- Citations: 70
Facer P, Atherton D, Roberts K, et al., 2006, A new syndrome of congenital insensitivity to pain diagnosed by skin biopsy and contact heat evoked potentials (CHEPS), Spring Meeting of the Association-of-British-Neurologists, Publisher: B M J PUBLISHING GROUP, Pages: 1400-1400, ISSN: 0022-3050
Atherton D, Taherzadeh O, Facer P, et al., 2006, The role of nerve growth factor in painful neuromas and the mechanism of pain relief by their relocation to muscle, Spring Meeting of the Association-of-British-Neurologists, Publisher: B M J PUBLISHING GROUP, Pages: 1391-1391, ISSN: 0022-3050
Daghir A, Anand P, Gabra H, 2006, Drug-induced exacerbation of glomus tumour pain, JOURNAL OF HAND SURGERY-BRITISH AND EUROPEAN VOLUME, Vol: 31B, Pages: 692-692, ISSN: 0266-7681
Irwin MS, Jain A, Anand P, et al., 2006, Free Innervated Sole of Foot Transfer for Contralateral Lower Limb Salvage, PLASTIC AND RECONSTRUCTIVE SURGERY, Vol: 118, Pages: 93E-97E, ISSN: 0032-1052
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- Citations: 4
Mukerji G, Yiangou Y, Agarwal SK, et al., 2006, Transient receptor potential vanilloid receptor subtype 1 in painful bladder syndrome and its correlation with pain, JOURNAL OF UROLOGY, Vol: 176, Pages: 797-801, ISSN: 0022-5347
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- Citations: 40
Mukerji G, Yiangou Y, Grogono J, et al., 2006, Localization of M<sub>2</sub> and M<sub>3</sub> muscarinic receptors in human bladder disorders and their clinical correlations, JOURNAL OF UROLOGY, Vol: 176, Pages: 367-373, ISSN: 0022-5347
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- Citations: 121
Anand U, Otto WR, Casula MA, et al., 2006, The effect of neurotrophic factors on morphology, TRPV1 expression and capsaicin responses of cultured human DRG sensory neurons, NEUROSCIENCE LETTERS, Vol: 399, Pages: 51-56, ISSN: 0304-3940
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- Citations: 88
Mukerji G, Yiangou Y, Corcoran SL, et al., 2006, Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations, BMC Urology, Vol: 6, ISSN: 1471-2490
BACKGROUND: The recent identification of the cold-menthol sensory receptor (TRPM8; CMR1), provides us with an opportunity to advance our understanding of its role in the pathophysiology of bladder dysfunction, and its potential mediation of the bladder cooling reflex. In this study, we report the distribution of the cool and menthol receptor TRPM8 in the urinary bladder in patients with overactive and painful bladder syndromes, and its relationship with clinical symptoms. METHODS: Bladder specimens obtained from patients with painful bladder syndrome (PBS, n = 16), idiopathic detrusor overactivity (IDO, n = 14), and asymptomatic microscopic hematuria (controls, n = 17), were immunostained using specific antibodies to TRPM8; nerve fibre and urothelial immunostaining were analysed using fibre counts and computerized image analysis respectively. The results of immunohistochemistry were compared between the groups and correlated with the Pain, Frequency and Urgency scores. RESULTS: TRPM8-immunoreactive staining was observed in the urothelium and nerve fibres scattered in the suburothelium. The nerve fibre staining was seen in fine-calibre axons and thick (myelinated) fibres. There was marked increase of TRPM8-immunoreactive nerve fibres in IDO (P = 0.0249) and PBS (P < 0.0001) specimens, compared with controls. A significantly higher number of TRPM8-immunoreactive axons were also seen in the IDO (P = 0.0246) and PBS (P < 0.0001) groups. Urothelial TRPM8 and TRPM8-immunoreactive thick myelinated fibres appeared unchanged in IDO and PBS. The relative density of TRPM8-immunoreactive nerve fibres significantly correlated with the Frequency (r = 0.5487, P = 0.0004) and Pain (r = 0.6582, P < 0.0001) scores, but not Urgency score. CONCLUSION: This study demonstrates increased TRPM8 in nerve fibres of overactive and painful bladders, and its relationship with clinical symptoms. TRPM8 may play a role in the symptomatology and pathophysiology of these disorders, and may
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