Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Stimulator

  • cord stimulator
  • nerve stimulator
  • peripheral nerve stimulator
  • potent stimulator
  • spinal cord stimulator
  • vagal nerve stimulator
  • vagus nerve stimulator

  • Selected Abstracts

    (615) Combined Use of Cervical Spinal Cord Stimulator (SCS) and Occipital Nerve Stimulator (ONS)

    PAIN MEDICINE, Issue 2 2000
    Article first published online: 25 DEC 200
    Author: Y. Eugene Mironer, Carolinas Center for Advanced Management of Pain A 51-year-old female patient was referred to the clinic in March 1997 with severe cervicalgia and right shoulder girdle pain. She rated her pain at 9/10 on a Visual Analog Scale (VAS). MRI showed multilevel severe spondylosis with significant neural foraminal stenosis at 3 levels. Multiple modalities of treatment (physiotherapy, epidural steroid injections, cervical plexus blocks) and a variety of medications (opioids, NSAIDs, anticonvulsants, antidepressants, etc.) failed to provide any improvement. The patient twice consulted neurosurgeons but was considered a poor surgical candidate. Finally, in July 1997, after a successful trial, a cervical SCS was implanted with the tip of the lead at level C2, achieving excellent coverage of the pain area. For the next 18 months the patient continued to do well, having minimal neck and shoulder discomfort and using only occasional oral analgesics. However, by January 1999, she developed intractable right-sided occipital neuralgia. Occipital nerve blocks were providing extremely short-term relief and the intake of different analgesics, including opioids, started to increase. In March 1999, after successful trial, an ONS was implanted. Unfortunately, it migrated shortly after implantation and had to be revised and re-anchored. After this procedure all headaches were completely controlled without medications. The patient continues to be very active, uses both stimulators daily, does not take any analgesics and rates her pain at 0/10 to 1/10 on VAS. [source]

    Stop, You Are Both Right: A Role for Both the Nerve Stimulator and Ultrasound-Guided Regional Anesthesia Techniques

    PAIN PRACTICE, Issue 2 2006
    Andrew D. Rosenberg MD
    No abstract is available for this article. [source]

    Artificial Manipulation of Voice in the Human by an Implanted Stimulator

    THE LARYNGOSCOPE, Issue 10 2008
    FACS, Michael Broniatowski MD
    Abstract Objectives/Hypothesis: Traditional approaches influencing voice quality (e.g., anatomical and chemical denervation for spasmodic dysphonia, surgical medialization for paralysis) have ignored the dynamic nature of the larynx. Study Design: We report here the first attempt to manipulate voice using an implanted stimulator to systematically control vocal fold adduction. Methods: Devices placed for aspiration in three subjects retaining speech after stroke, cerebral palsy, and multiple sclerosis were used to stimulate recurrent laryngeal nerves with 42 Hz, 52 to 200 microsecond pulses of incremental amplitudes during phonation with the tracheostomy tube occluded. Vocal fold adduction increased with stimulation strength (P < .05). Speech was analyzed with the Vox Metria program. Results: We found highly significant differences for fundamental frequency (P < .007), jitter (P < .004), and shimmer (P < .005), between natural and stimulated voice (aah and eeh) when using higher charges. Conclusions: Dynamic vocal fold manipulation seems promising in terms of versatility lacking with static approaches to voice control. [source]

    Adventures in multivalency, the Harry S. Fischer memorial lecture CMR 2005; Evian, France

    Michael F. Tweedle
    Abstract This review discusses multivalency in the context of drug discovery, specifically the discovery of new diagnostic imaging and related agents. The aim is to draw attention to the powerful role that multivalency plays throughout research involving molecular biology, in general, and much of biochemically targeted contrast agent research, in particular. Two examples from the author's laboratory are described. We created small (,5,kDa) peptide ,dimers' composed of two different, chemically linked peptides. The monomer peptides both bound to the same target protein with Kd,,,100,s,nM, while the heterodimers had sub-nM Kd values. Biological activity was evident in the heterodimers where none or very little existed in homodimers, monomers or monomer mixtures. Two different tyrosine kinases (KDR and C-Met) and four peptide families produced consistent results: multivalent heterodimers were uniquely different. The second example begins with making two micron ultrasound bubbles coated with the peptide, TKPPR (a Tuftsin antagonist) as a negative control for bubbles targeted with angiogenesis target-binding peptides. Unexpected binding of a ,negative' control, (TKPPR)-targeted bubble to endothelial cells expressing angiogenesis targets, led to the surprising result that TKPPR, only when multimerized, binds avidly, specifically and actively to neuropilin-1, a VEGF co-receptor. VEGF is the primary stimulator of angiogenesis. Tuftsin is a small peptide (TKPR) derived from IgG that binds to macrophages during inflammation, and has been studied for over 30 years. The receptor has never been cloned. The results led to new conclusions about Tuftsin, neuropilin-1 and the purpose, up to now unknown, of exon 8 in VEGF. Multivalency can be used rationally to solve practical problems in drug discovery. When targeting larger structures, multivalency is frequently unavoidable, and can lead to unpredictable and useful biochemical information, as well as to new drug candidates. Copyright © 2006 John Wiley & Sons, Ltd. [source]

    Coexistence of Idiopathic Rolandic Epilepsy and CSWS in Two Families

    EPILEPSIA, Issue 10 2006
    Xavier De Tiège
    Summary:,Purpose: To report two families combining benign childhood epilepsy with centrotemporal spikes (BCECS) and cryptogenic epilepsy with continuous spike,waves during sleep (CSWS) in first-degree relatives. Methods: Clinical, EEG, and cerebral imaging data are described. Results: Family 1: The proband was 3 years old at epilepsy onset. First seizures were convulsive, with centrotemporal spikes on EEG. At age 5 years, he had complex partial seizures, psychomotor regression, and centrotemporal CSWS. [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) showed left parietal hypermetabolism. After several antiepileptic drug (AED) trials, valproate (VPA) and ethosuximide (ESM) induced seizure remission, CSWS disappearance, and psychomotor improvement. Learning disabilities, however, persisted. Family history was remarkable for BCECS in his father. Family 2: The proband was 2 years old at epilepsy onset. First seizures were convulsive, with centrotemporal CSWS on EEG. Despite several AED trials including corticosteroids, focal negative myoclonia, atypical absences, and psychomotor regression occurred, leading to severe mental retardation. FDG-PET showed bilateral parietal hypermetabolism. Vagus nerve stimulator was implanted. Her family history was remarkable for BCECS in her father and febrile convulsions in infancy in her mother. Conclusions: These data suggest the existence of a common genetic basis between BCECS and cryptogenic epilepsies with CSWS. The higher expression in patients with CSWS could be related to other genetic or acquired factors. These data suggest that these epileptic syndromes constitute edges of a continuum. [source]

    Historical Aspects of Idiopathic Generalized Epilepsies

    EPILEPSIA, Issue 2005
    Peter Wolf
    Summary:, Early in these proceedings, the origin of the three terms in the title, "idiopathic generalized epilepsy," is discussed with respect to their significance over time, and typical misunderstandings. In the mid-20th century, a rather chaotic use of a multitude of often loosely defined terms had developed, which increasingly became an obstacle to a meaningful international discussion. The International League against Epilepsy (ILAE) took the initiative to develop an internationally accepted terminology with a classification system consisting of a classification of seizures (1981) and a classification of syndromes (1989). The Idiopathic Generalized Epilepsies are one of its four major groups emerging from a double dichotomy of generalized versus localization-related and idiopathic versus symptomatic. The inclusion of biologic aspects such as syndrome-specific ages of onset ("age-related syndromes") or syndrome-specific relations of seizure occurrence to the sleep,wake cycle ("Epilepsy with Grand Mal on Awaking") meant that the syndrome classification merged the more biological views of the German school with the more neurophysiological ones of the French. Apart from establishing a common international language concerning epilepsy, the International Classification of Epilepsies and Epileptic Syndromes became an important stimulator of research, especially concerning the idiopathic epilepsies. In particular, genetic and functional imaging investigations aim at a better understanding of these conditions. It is now understood that most idiopathic syndromes have a,sometimes complex,genetic background, but we are also becoming aware of the inappropriateness of the time-honored term "generalized" and part of our dichotomies. Both localization-related and "generalized" idiopathic epilepsies seem to share a principle of ictogenesis based on functional anatomic pathogenic networks, and we seem to move toward understanding them as functional system disorders of the brain. [source]

    Development of Amygdaloid Kindling in Histidine Decarboxylase,deficient and Histamine H1 Receptor,deficient Mice

    EPILEPSIA, Issue 4 2004
    Tadashi Hirai
    Summary: Purpose: This study attempted to clarify the role of histamine or histamine H1 receptors in the development of amygdaloid kindling by using histidine decarboxylase (HDC)-deficient and histamine H1 receptor (H1R)-deficient mice. Methods: Under pentobarbital anesthesia, mice were fixed to a stereotaxic apparatus, and bipolar electrodes were implanted into the right amygdala. Electrodes were connected to a miniature receptacle, which was embedded in the skull with dental cement. A bipolar electroencephalogram was recorded; bipolar stimulation of the amygdala was applied every day with a constant-current stimulator and continued until a generalized convulsion was obtained. Results: The development of amygdaloid kindling in HDC-deficient and H1R-deficient mice was significantly accelerated compared with that in their respective wild-type mice. In addition, the afterdischarge (AD) duration and generalized seizure duration in HDC-deficient and H1R-deficient mice were prolonged. Intraperitoneal injection of histidine resulted in an inhibition of amygdaloid kindled seizures in wild-type mice at doses that caused an increase in the histamine contents of the brain. However, no significant effect was observed with histidine in H1R-deficient mice at the same dose. Conclusions: These findings suggest that histaminergic mechanisms through H1 receptors play a crucial role not only in amygdaloid kindled seizures but also in the development of amygdaloid kindling. [source]

    Photosensitivity in Relation to Epileptic Syndromes: A Survey from an Epilepsy Center in Japan

    EPILEPSIA, Issue 3 2001
    Hideaki Shiraishi
    Summary: ,Purpose: We examined the incidence and distribution of photosensitivity among the different age groups and different types of epilepsies and epileptic syndromes. Furthermore, we considered the influence of ethnic and geographic factors on the incidence of photoparoxysmal response (PPR) in epilepsy patients. Methods: We analyzed the responses to intermittent photic stimulation (IPS) by using a Grass PS22 or PS33 photic stimulator for in 2,187 unselected patients with epilepsy who were treated in our center. Results: The classic PPR was elicited in 37 (1.7%) patients. The mean age of these 37 patients was 17.0 years. The subpopulation of patients having PPR included 2.0% of all patients with symptomatic generalized epilepsy, 5.6% (p < 0.01) of those with idiopathic generalized epilepsy, 0.7% of those with symptomatic localization-related epilepsy, and 2.9% of those with undetermined epilepsy. PPR accounted for 17.4 % (p < 0.01) of the patients with juvenile myoclonic epilepsy, 7.6% (p < 0.01) of those with grand mal on awakening, and 6.1% (p < 0.01) of those with symptomatic occipital lobe epilepsy. The incidence of PPR increased in patients up to age 15 years, and suddenly decreased after age 20 years. Conclusion: The present study presents the first report from eastern Asia, analyzing the incidence of PPR with a restricted definition comparable to the other studies, and the rate of PPR was relatively low compared with the studies performed in the European countries. We could confirm the clear relation between age and positive PPR. [source]

    Effects of Vagus Nerve Stimulation on Progressive Myoclonus Epilepsy of Unverricht-Lundborg Type

    EPILEPSIA, Issue 8 2000
    Brien Smith
    Summary: Purpose: A 34-year-old woman with progressive myoclonus epilepsy of Unverricht-Lundborg type was considered for vagus nerve stimulation (VNS) therapy. Methods: After demonstration of intractability to multiple antiepileptic regimens and progressive deterioration in cerebellar function, the patient was implanted with a vagus nerve stimulator and followed for 1 year. Neurological status, seizure frequency, and parameter changes were analyzed. Results: VNS therapy resulted in reduction of seizures (more than 90%) and a significant improvement in cerebellar function demonstrated on neurological examination. The patient reported improved quality of life based in part on her ability to perform activities of daily living. Conclusions: VNS therapy may be considered a treatment option for progressive myoclonus epilepsy. The effects of VNS on seizure control and cerebellar dysfunction may provide clues to the underlying mechanism(s) of action. [source]

    Considerations for pacing of the cricoarytenoid dorsalis muscle by neuroprosthesis in horses

    Summary Reasons for performing study: The success rate of prosthetic laryngoplasty is limited and may be associated with significant sequelae. Nerve muscle pedicle transplantation has been attempted but requires a year before function is restored. Objective: To determine the optimal parameters for functional electrical stimulation of the recurrent laryngeal nerve in horses. Methods: An experimental in vivo study was performed on 7 mature horses (2,21 years). A nerve cuff was placed on the distal end of the common trunk of the recurrent laryngeal nerve (RLN). In 6 horses the ipsilateral adductor branch of RLN was also transected. The electrodes were connected to programmable internal stimulator. Stimulation was performed using cathodic phase and then biphasic pulses at 24 Hz with a 0.427 ms pulse duration. Stimulation-response experiments were performed at monthly intervals, from one week following implantation. The study continued until unit failure or the end of project (12 months). Two of the horses were stimulated continuously for 60 min to assess onset of fatigue. Results: Excellent arytenoid cartilage abduction (mean arytenoid angle of 52.7°, range 48.5,56.2°) was obtained in 6 horses (laryngeal grades I or II (n = 3) and III (n = 2). Poor abduction was obtained in grade IV horses (n = 2). Arytenoid abduction was maintained for up to a year in one horse. Technical implant failure resulted in loss of abduction in 6 horses at one week to 11 months post operatively. Mean tissue impedance was 1.06 kOhm (range 0.64,1.67 kOhm) at one week, twice this value at 2 months (mean 2.32, range 1.11,3.75 kOhm) and was stable thereafter. Maximal abduction was achieved at a stimulation range of 0.65,7.2 mA. No electrical leakage was observed. Constant stimulation of the recurrent laryngeal nerve for 60 min led to full abduction without evidence of muscle fatigue. Conclusions: Functional electrical stimulation of the recurrent laryngeal nerve leading to full arytenoid abduction can be achieved. The minimal stimulation amplitude for maximal abduction angle is slightly higher than those for man and dogs. Clinical relevance: This treatment modality could eventually be applicable to horses with recurrent laryngeal neuropathy. [source]

    A New and Productive Route to 1-Heteroarylcyclopropanols

    Vladimir N. Belov
    Abstract (E/Z)-2-(1-Allyloxycyclopropyl)-3-methoxyacrylonitrile (4 -All) was designed and prepared in five steps (58% overall yield) from ethyl cyclopropylidenacetate as a valuable precursor to various 1-heteroarylcyclopropanols. Its condensation with amidines, guanidine, hydrazine, and methyl thioglycolate and subsequent removal of the allyl protecting group yields 1-heteroarylcyclopropanols such as 1 -OH (36% over 2 steps), a very potent NO-independent stimulator of soluble guanylate cyclase. Direct cleavage of the allyl ether protecting group [by palladium-catalyzed substitution with lithium p -toluenesulfinate in AcOH or treatment with c -HexMgBr/Ti(OiPr)4] gives highly functionalized, sterically congested 1-heteroarylcyclopropanols 29, 30, and 34 with intact amino and ester groups. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source]

    Hepatitis C virus escape from the interferon regulatory factor 3 pathway by a passive and active evasion strategy,

    HEPATOLOGY, Issue 5 2007
    Marco Binder
    Hepatitis C virus (HCV) has been known to replicate with extremely varying efficiencies in different host cells, even within different populations of a single human hepatoma cell line, termed Huh-7. Several reports have implicated the retinoic-acid inducible gene I (RIG-I)/ interferon regulatory factor 3 (IRF-3) pathway of the innate antiviral response with differences in host cell permissiveness to HCV. To investigate the general impact of the IRF-3 response onto HCV replication in cell culture, we generated an ample array of stable Huh-7 cell lines with altered IRF-3 responsiveness. Neither blocking IRF-3 activation in various host cells by expression of dominant negative RIG-I or HCV NS3/4A protease nor reconstitution of RIG-I signaling in Huh7.5, a cell clone known to be defective in this pathway, had any impact on HCV replication. Only by overexpressing constitutively active RIG-I or the signaling adaptor Cardif (also known as interferon-beta promoter stimulator 1, mitochondrial anti-viral signaling protein, or virus-induced signaling adaptor), both leading to a stimulation of the IRF-3 pathway in the absence of inducers, was HCV replication significantly inhibited. We therefore assessed the extent of RIG-I, dependent IRF-3 activation by different species of RNA, including full-length HCV genomes and HCV RNA duplexes, and observed strong induction only in response to double-stranded RNAs. Conclusion: Based on these findings, we propose a refined model of innate immune escape by HCV involving limited initial induction and stringent subsequent control of the IRF-3 response. (HEPATOLOGY 2007.) [source]

    Fibrosis in heart disease: understanding the role of transforming growth factor-,1 in cardiomyopathy, valvular disease and arrhythmia

    IMMUNOLOGY, Issue 1 2006
    Razi Khan
    Summary The importance of fibrosis in organ pathology and dysfunction appears to be increasingly relevant to a variety of distinct diseases. In particular, a number of different cardiac pathologies seem to be caused by a common fibrotic process. Within the heart, this fibrosis is thought to be partially mediated by transforming growth factor-,1 (TGF-,1), a potent stimulator of collagen-producing cardiac fibroblasts. Previously, TGF-,1 had been implicated solely as a modulator of the myocardial remodelling seen after infarction. However, recent studies indicate that dilated, ischaemic and hypertrophic cardiomyopathies are all associated with raised levels of TGF-,1. In fact, the pathogenic effects of TGF-,1 have now been suggested to play a major role in valvular disease and arrhythmia, particularly atrial fibrillation. Thus far, medical therapy targeting TGF-,1 has shown promise in a multitude of heart diseases. These therapies provide great hope, not only for treatment of symptoms but also for prevention of cardiac pathology as well. As is stated in the introduction, most reviews have focused on the effects of cytokines in remodelling after myocardial infarction. This article attempts to underline the significance of TGF-,1 not only in the post-ischaemic setting, but also in dilated and hypertrophic cardiomyopathies, valvular diseases and arrhythmias (focusing on atrial fibrillation). It also aims to show that TGF-,1 is an appropriate target for therapy in a variety of cardiovascular diseases. [source]

    Use of the sensory nerve stimulator to accelerate healing of a venous leg ulcer with sensory nerve dysfunction: a case study

    Article first published online: 7 SEP 200
    Utilisation d'un stimulateur nerveux sensitif pour accélerer la cicatrisation des ulcères veineux avec dysfonctionnement nerveux sentitif: à propos d'un cas Un nouveau traitement utilisant la stimulation nerveuse sensitive (International Patent Appliction Number PCT/AU2004/001079 , nerve dysfunction and tissue healing"(Khalil Z) a été développé dans notre laboratoire de physiologie vasculaire. Ce traitemeent a montré une amélioration de la fonction nerveuse sensitive et les déficiences en cicatrisation associées chez des personnes agées par rapport à des personnes jeunes. Un homme de 82 ans présentant un ulcère de jambe petit mais persistant depuis 18 mois, en dépit d'un traitement approprié en pansements et en contention., a été vu dans un service specialisé en traitement des plaies. Les functions sensitives et microvasculaires etaient évaluées avec beaucoup de details gràce à l'utilisation de techniques de laboratoire de physiologie vasculaire, et il a bénéficié d'un traitement par stimulation en complément d'un traitement conventionnel. Sa plaie a cicatrisé après 4 semaines. Nous rapportons ce cas ici. Avant traitement par stimulation nerveuse, la sensation cutanée, le flux sanguin microcirculatoire et la tension d'oxygène ont été trouvées diminuées près de l'ulcère en comparaison avec le membre oppose non ulcéré. Après traitement, la tension d'oxygène et la flux sanguin microcirculatoire étaient améliorés. Ce cas apporte une preuve supplémentaire que le traitement par stimulation nerveuse sensitive dans des conditions bien définies améliore la cicatrisation. L'observation d'une amélioration de la fonction nerveuse sensitive supporte la nition qu'une amélioration de la cicatrisation est liée à une amélioration de la fonction nerveuse. Anwendung eines sensiblen Nervenstimulationsgerätes zur beschleunigten Wundheilung eines venösen Beinulcus mit begleitender neurologischer Dysfunktion: eine Fallstudie Eine neue Therapieform zur Stimulation der Nervensensibilität wurde in den eigenen Laboratorien entwickelt. Diese Behandlungsform zeigte eine Verbesserung der insbesondere bei älteren Patienten vorliegenden eingeschränkten Nervenfunktion und der damit verbundenen verzögerten Wundheilung. Wir berichten über den Fall eines 82 jährigen Patienten mit einem kleinen, über 18 Monaten persistierenden venösen Ulkus am Unterschenkel trotz Anwendung verschiedener Wundauflagen und einer begleitenden Kompressionsbehandlung. In unserem Labor wurden unter Anwendung vaskulärerer und physiologsicher Messungen die Sensibilität und die mikrovaskuläre Funktion erfasst und eine Nervenstimulationstherapie in Verbindung mit Wundauflagen und Kompressionsbehandlung durchgeführt. Die Wundheilung war nach 4 Wochen abgeschlossen. Vor der Nervenstimulationstherapie war die Hautsensibilität, der mikrovaskuläre Blutfluss sowie der Sauerstoffdruck im Gewebe im Vergleich zur gesunden Gegenseite vermindert. Nach der Therapie zeigten sich alle drei Parameter verbessert. Dieser Fall stellt einen weiteren Beweis dar, dass eine zusätzliche Nervenstimulation zu den etablierten Behandlungsstrategien die Wundheilung positiv beeinflusst. Die Beobachtung dass sich die sensible Nervenfunktion verbessert hat lässt zusätzlich den Schluss zu, dass eine Optimierung der Wundheilung auch durch eine verbesserte Nervenfunktion erreicht wird. Impiego della stimolazione di nervi sensoriali per accelerare la guarigione di ulcere venose della gamba con disfunzione dei nervi sensoriali: studio di un caso Nel nostro laboratorio di fisiologia vascolare è stata sviluppata una nuova terapia che utilizza la stimolazione dei nervi sensoriali (brevetto internazionale di applicazione numero: PCT/AU2004/001079: riparazione del tessuto e della funzione del nervo (Khalil, Z). Questo trattamento ha mostrato di migliorare la carente funzione dei nervi sensoriali e la ridotta riparazione tessutale di ferite in persone anziane se paragonate ai livelli di guarigione di persone giovani.. Un uomo di 82 anni con una piccola ma persistente ulcera delle gambe presente da 18 mesi, nonostante un apparente ed appropriato trattamento con medicazioni e compressione, è stato visitato in un servizio specialistico per la cura delle ferite. Le funzioni sensoriali del paziente e la microcircolazione sono state monitorizzate in grande dettaglio utilizzando le tecniche del laboratorio di fisiologia vascolare, ed è stata fornita la terapia di stimolazione dei nervi sensoriali in aggiunta alla terapia convenzionale.. La sua ferita è guarita in quattro settimane. Noi riportiamo qui un caso. Prima del trattamento con stimolazione dei nervi, sono state riscontrate ridotte la sensibilità cutanea, il flusso ematico microcircolatorio e la tensione di ossigeno vicino alla lesione ulcerativa, se comparate con la sede controlaterale non ulcerata. Dopo la terapia, la tensione di ossigeno ed il flusso microcircolatorio sono migliorati. Questo caso fornisce una ulteriore evidenza che la terapia con stimolazione del sensorio migliora la riparazione tessutale di ferite seguendo determinati parametri. L'osservazione di una migliore funzione sensoriale fornisce supporto per la nozione che una migliore riparazione tessutale è mediata da una migliore funzionalità dei nervi. Uso del estimulador nervioso sensitivo para acelerar la cicatrización de una úlcera vascular venosa con disfunción nerviosa sensitiva: estudio de un caso En nuestro laboratorio de fisiología vascular se ha desarrollado un nuevo tratamiento basado en la estimulación nerviosa sensitiva [Número de Solicitud de Patente Internacional: PCT/AU2004/001079: ,Función nerviosa y cicatrización tisular"(Khalil, Z)]. Se ha comprobado que este tratamiento mejora la función nerviosa sensitiva deficiente y la subsiguiente curación deficiente de heridas en personas de edad avanzada hasta alcanzar los niveles observados en personas jóvenes. En un servicio de tratamiento de heridas especializado se visitó a un hombre de 82 años con una úlcera vascular venosa pequeña, pero persistente durante 18 meses a pesar de la aplicación de apósitos aparentemente apropiados y tratamiento compresivo. Se evaluaron muy por debajo las funciones sensitiva y microvascular del paciente por medio de técnicas de laboratorio de fisiología vascular y se le aplicó tratamiento de estimulación nerviosa sensitiva además de tratamiento convencional. Su herida curó al cabo de 4 semanas. En este artículo describimos el caso. Antes de proceder al tratamiento de estimulación nerviosa se comprobó que la sensibilidad cutánea, el flujo sanguíneo microvascular y la concentración de oxígeno estaban reducidos en la proximidad de la úlcera en comparación con la pierna contralateral, no ulcerada. Después del tratamiento, la concentración de oxígeno y el flujo sanguíneo microvascular habían mejorado. Este caso proporciona pruebas adicionales de que el tratamiento de estimulación nerviosa sensitiva, con los parámetros especificados, mejora la curación de las heridas. La observación de la mejoría de la función nerviosa sensitiva respalda el concepto de que la mediación de una cicatrización más óptima reside en la mejoría de la función nerviosa. Användandet av känselnerv stimulator för att påskynda läkning av venösa bensår med känselnerv dysfunktion: en fallstudie En ny terapi som använder känselnerv stimulering [Internationellt Patent Ansökningsnummer PCT/AU2004/001079: ,nervfunktion och vävnadsläkning'(Khalil, Z)] har utvecklats i vårt laboratorium för vaskulär fysiologi. Denna behandling har visat sig förbättra försämrad känselnervfunktion och ansluten nedsatt sårläkning hos äldre personer till nivåer iakttagna hos yngre personer. En 82-årig man med ett litet venöst bensår som emellertid fortbestått i 18 månader, trots klart tillbörliga sårförband och kompressionsterapi, sågs på en specialist sårvårdsmottagning. Patientens känslofunktion och mikrovskulära funktion undersöktes ingående med hjälp av vaskulärfysiologiska laboratorie tekniker, och han erhöll känselnerv stimuleringsterapi samt konventionell terapi. Hans sår läktes efter 4 veckor. Vi rapporterar detta fall här. Jämfört med det andra sårfria benet iakttogs i området runt såret nedsatt känsla i huden, nedsatt mikrovaskulärt blodflöde och syre tryck före insättandet av nervstimuleringsterapi. Efter terapin hade syretrycket och mikrovaskulära blodflödet förbättrats. Denna fallstudie utgör ett ytterligare bevis för att känselnerv stimuleringsterapi förbättrar sårläkning i de parameter som stipulerats. Observationen att känselnervfunktionen förbättrades utgör ett stöd för uppfattningen att förbättrad nervfunktion åstadkommer förbättrad sårläkning. [source]

    Neurolytic phenol blockade of the obturator nerve for severe adductor spasticity

    Background: In this study, we present the 3-month follow-up results of a retrospective analysis of obturator nerve (ON) phenol neurolysis performed between 2000 and 2007 in patients with adductor spasticity. Methods: The study was performed by retrospective investigation of the clinical follow-up results of 80 ON phenol treatments in 62 patients. Neurolysis using 5,10 ml 6% phenol was applied with the guidance of fluoroscopy and a peripheral nerve stimulator. Pain, spasticity and hygiene were evaluated and the hip abduction range of motion (ROM) was measured at the end of the first week and in the first, second and third months following the intervention. Results: The visual analogue scale scores decreased significantly in the first week, first month and the second month, but reached their initial values in the third month. A drastic increase in the ROM values was shown in hip abduction in the first week, first month and second month. An increase in the Ashworth Scale values was observed in the second and third months, but they did not reach their initial values. The hygiene score decreased drastically in the first week and the first and second months, but worsened in the third month. The success rate in nerve localization during ON neurolysis was 100%. Conclusion: ON phenol blockade with fluoroscopy and peripheral nerve stimulator guidance in patients with adductor spasticity led to a decrease in spasticity and pain with an increase in the ROM of the hip and better hygiene with an efficacy lasting for about 3 months. [source]

    Thyroid hormone-mediated growth and differentiation of growth plate chondrocytes involves IGF-1 modulation of ,-catenin signaling

    Lai Wang
    Abstract Thyroid hormone regulates terminal differentiation of growth plate chondrocytes in part through modulation of the Wnt/,-catenin signaling pathway. Insulin-like growth factor 1 (IGF-1) has been described as a stabilizer of ,-catenin, and thyroid hormone is a known stimulator of IGF-1 receptor expression. The purpose of this study was to test the hypothesis that IGF-1 signaling is involved in the interaction between the thyroid hormone and the Wnt/,-catenin signaling pathways in regulating growth plate chondrocyte proliferation and differentiation. The results show that IGF-1 and the IGF- receptor (IGF1R) stimulate Wnt-4 expression and ,-catenin activation in growth plate chondrocytes. The positive effects of IGF-1/IGF1R on chondrocyte proliferation and terminal differentiation are partially inhibited by the Wnt antagonists sFRP3 and Dkk1. T3 activates IGF-1/IGF1R signaling and IGF-1-dependent PI3K/Akt/GSK-3, signaling in growth plate chondrocytes undergoing proliferation and differentiation to prehypertrophy. T3 -mediated Wnt-4 expression, ,-catenin activation, cell proliferation, and terminal differentiation of growth plate chondrocytes are partially prevented by the IGF1R inhibitor picropodophyllin as well as by the PI3K/Akt signaling inhibitors LY294002 and Akti1/2. These data indicate that the interactions between thyroid hormone and ,-catenin signaling in regulating growth plate chondrocyte proliferation and terminal differentiation are modulated by IGF-1/IGF1R signaling through both the Wnt and PI3K/Akt signaling pathways. While chondrocyte proliferation may be triggered by the IGF-1/IGF1R-mediated PI3K/Akt/GSK3, pathway, cell hypertrophy is likely due to activation of Wnt/,-catenin signaling, which is at least in part initiated by IGF-1 signaling or the IGF-1-activated PI3K/Akt signaling pathway. © 2010 American Society for Bone and Mineral Research [source]

    Osteoblastic Tartrate-Resistant Acid Phosphatase: Its Potential Role in the Molecular Mechanism of Osteogenic Action of Fluoride,

    K-H William Lau
    Abstract Although type 5 TRACP is recognized as a histochemical and biochemical marker of osteoclasts, there is evidence that bone forming cells, osteoblasts, and osteocytes also express a type 5 TRACP. Accordingly, an osteoblastic type 5 TRACP has been purified from human osteoblasts and from bovine cortical bone matrices. Comparison of biochemical properties of osteoblastic type 5 TRACP with those of osteoclastic type 5 TRACP suggests that osteoblastic type 5 TRACP is a different isoenzyme from osteoclastic type 5 TRACP. Two properties of osteoblastic type 5 TRACP may be relevant to its physiological functions: (1) it acts as a protein-tyrosine phosphatase (protein tyrosine phosphorylation) under physiologically relevant conditions, and (2) it is sensitive to inhibition by clinically relevant concentrations of fluoride. Because fluoride is a stimulator of osteoblastic proliferation and differentiation and a potent osteogenic agent and because protein tyrosine phosphorylation plays an important regulatory role in cell proliferation and differentiation, these unique properties and other evidence summarized in this review led to the proposal that the osteogenic action of fluoride is mediated, at least in part, by the fluoride-mediated inhibition of osteoblastic type 5 TRACP/protein tyrosine phosphorylation, which leads to a stimulation of osteoblast proliferation and differentiation, and subsequently, an increase in bone formation. [source]

    The Structural and Hormonal Basis of Sex Differences in Peak Appendicular Bone Strength in Rats,,

    Bom-Taeck Kim
    Abstract To identify the structural and hormonal basis for the lower incidence of fractures in males than females, sex differences in femoral mid-shaft geometry and breaking strength were studied in growth hormone (GH)-replete and -deficient male and female rats. Sexual dimorphism appeared during growth. Cortical thickening occurred almost entirely by acquisition of bone on the outer (periosteal) surface in males and mainly on the inner (endocortical) surface in females. By 8 months of age, males had 22% greater bone width and 33% greater breaking strength than females. Gonadectomy (Gx) at 6 weeks reduced sex differences in bone width to 7% and strength to 21% by halving periosteal bone formation in males and doubling it in females. Gx had no net effect on the endocortical surface in males but abolished endocortical bone acquisition in females. GH deficiency halved periosteal bone formation and had no net effect on the endocortical surface in males, but abolished bone acquisition on both surfaces in females, leaving males with 17% greater bone width and 44% greater breaking strength than females. Sex hormone deficiency produces greater bone fragility in males than females by removing a stimulator of periosteal growth in males and removing an inhibitor of periosteal growth in females. GH deficiency produces less bone fragility in males than females because males retain androgen-dependent periosteal bone formation while bone acquisition on both surfaces is abolished in females. Thus, periosteal growth is independently and additively stimulated by androgens and GH in males, inhibited by estrogen, and stimulated by GH in females. The hormonal regulation of bone surfaces establishes the amount and spatial distribution of bone and so the sexual dimorphism in its strength. [source]

    Prostaglandin E2 inhibits the proliferation of human gingival fibroblasts via the EP2 receptor and Epac

    Evgeny Weinberg
    Abstract Elevated levels of prostaglandins such as PGE2 in inflamed gingiva play a significant role in the tissue destruction caused by periodontitis, partly by targeting local fibroblasts. Only very few studies have shown that PGE2 inhibits the proliferation of a gingival fibroblast (GF) cell line, and we expanded this research by using primary human GFs (hGFs) and looking into the mechanisms of the PGE2 effect. GFs derived from healthy human gingiva were treated with PGE2 and proliferation was assessed by measuring cell number and DNA synthesis and potential signaling pathways were investigated using selective activators or inhibitors. PGE2 inhibited the proliferation of hGFs dose-dependently. The effect was mimicked by forskolin (adenylate cyclase stimulator) and augmented by IBMX (a cAMP-breakdown inhibitor), pointing to involvement of cAMP. Indeed, PGE2 and forskolin induced cAMP generation in these cells. Using selective EP receptor agonists we found that the anti-proliferative effect of PGE2 is mediated via the EP2 receptor (which is coupled to adenylate cyclase activation). We also found that the effect of PGE2 involved activation of Epac (exchange protein directly activated by cAMP), an intracellular cAMP sensor, and not PKA. While serum increased the amount of phospho-ERK in hGFs by ,300%, PGE2 decreased it by ,50%. Finally, the PGE2 effect does not require endogenous production of prostaglandins since it was not abrogated by two COX-inhibitors. In conclusion, in human gingival fibroblasts PGE2 activates the EP2,cAMP,Epac pathway, reducing ERK phosphorylation and inhibiting proliferation. This effect could hamper periodontal healing and provide further insights into the pathogenesis of inflammatory periodontal disease. J. Cell. Biochem. 108: 207,215, 2009. © 2009 Wiley-Liss, Inc. [source]

    ATP and UTP at low concentrations strongly inhibit bone formation by osteoblasts: A novel role for the P2Y2 receptor in bone remodeling

    Astrid Hoebertz
    Abstract There is increasing evidence that extracellular nucleotides act on bone cells via multiple P2 receptors. The naturally-occurring ligand ATP is a potent agonist at all receptor subtypes, whereas ADP and UTP only act at specific receptor subtypes. We have reported that the formation and resorptive activity of rodent osteoclasts are stimulated powerfully by both extracellular ATP and its first degradation product, ADP, the latter acting at nanomolar concentrations, probably via the P2Y1 receptor subtype. In the present study, we investigated the actions of ATP, ADP, adenosine, and UTP on osteoblastic function. In 16,21 day cultures of primary rat calvarial osteoblasts, ADP and the selective P2Y1 agonist 2-methylthioADP were without effect on bone nodule formation at concentrations between 1 and 125 ,M, as was adenosine. However, UTP, a P2Y2 and P2Y4 receptor agonist, known to be without effect on osteoclast function, strongly inhibited bone nodule formation at concentrations ,,1 ,M. ATP was inhibitory at ,,10 ,M. Rat osteoblasts express P2Y2, but not P2Y4 receptor mRNA, as determined by in situ hybridization. Thus, the low-dose effects of extracellular nucleotides on bone formation and bone resorption appear to be mediated via different P2Y receptor subtypes: ADP, signalling through the P2Y1 receptor on both osteoclasts and osteoblasts, is a powerful stimulator of osteoclast formation and activity, whereas UTP, signalling via the P2Y2 receptor on osteoblasts, blocks bone formation by osteoblasts. ATP, the ,universal' agonist, can simultaneously stimulate resorption and inhibit bone formation. These findings suggest that extracellular nucleotides could function locally as important negative modulators of bone metabolism, perhaps contributing to bone loss in a number of pathological states. J. Cell. Biochem. 86: 413,419, 2002. © 2002 Wiley-Liss, Inc. [source]

    cAMP activation by PACAP/VIP stimulates IL-6 release and inhibits osteoblastic differentiation through VPAC2 receptor in osteoblastic MC3T3 cells

    Azusa Nagata
    The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the glucagon/vasoactive intestinal peptide (VIP) superfamily, stimulates cyclic AMP accumulation initiating a variety of biological processes such as: neurotropic actions, immune and pituitary function, learning and memory, catecholamine biosynthesis and regulation of cardiopulmonary function. Both osteoclasts and osteoblasts have been shown to express receptors for PACAP/VIP implicated in their role in bone metabolism. To further understand the role of PACAP/VIP family in controlling bone metabolism, we investigated differentiation model of MC3T3-E1 cells, an osteoblastic cell line derived from mouse calvaria. Quantitative RT-PCR analysis demonstrated that MC3T3-E1 cells expressed only VPAC2 receptor and its expression was upregulated during osteoblastic differentiation, whereas VPAC1 and PAC1 receptors were not expressed. Consistent with expression of receptor subtype, both PACAP and VIP stimulate cAMP accumulation in a time- and dose-dependent manner with the similar potency in undifferentiated and differentiated cells, while Maxadilan, a specific agonist for PAC1-R, did not. Furthermore, downregulation of VPAC2-R by siRNA completely blocked cAMP response mediated by PACAP and VIP. Importantly, PACAP/VIP as well as forskolin markedly suppressed the induction of alkaline phosphatase mRNA upon differentiation and the pretreatment with 2,,5,-dideoxyadenosine, a cAMP inhibitor, restored its inhibitory effect of PACAP. We also found that PACAP and VIP stimulated IL-6 release, a stimulator of bone resorption, and VPAC2-R silencing inhibited IL-6 production. Thus, PACAP/VIP can activate adenylate cyclase response and regulate IL-6 release through VPAC2 receptor with profound functional consequences for the inhibition of osteoblastic differentiation in MC3T3-E1 cells. J. Cell. Physiol. 221: 75,83, 2009. © 2009 Wiley-Liss, Inc [source]

    Vascular smooth muscle cell growth-promoting factor/F-spondin inhibits angiogenesis via the blockade of integrin ,v,3 on vascular endothelial cells

    Yoshito Terai
    Vascular smooth muscle cell growth-promoting factor (VSGP) was originally isolated from bovine ovarian follicular fluid as a stimulator of vascular smooth muscle cell proliferation. Homology searches indicate that bovine and human VSGPs are orthologs of rat F-spondin. Here, we examined whether recombinant human VSGP/F-spondin affected the biological activities of endothelial cells. VSGP/F-spondin did not affect the proliferation of human umbilical vein endothelial cells (HUVECs); however, it did inhibit VEGF- or bFGF-stimulated HUVEC migration. To clarify the mechanism of this inhibitory effect, we examined the adhesion of HUVECs to extracellular matrix proteins. VSGP/F-spondin specifically inhibited the spreading of HUVECs on vitronectin via the functional blockade of integrin ,v,3. As a result, VSGP/F-spondin inhibited the tyrosine phosphorylation of focal adhesion kinase (FAK) when HUVECs were plated on vitronectin. Moreover, VSGP/F-spondin inhibited the activation of Akt when HUVECs on vitronectin were stimulated with VEGF. VSGP/F-spondin inhibited tube formation by HUVECs in vitro and neovascularization in the rat cornea in vivo. These results indicate that VSGP/F-spondin inhibits angiogenesis at least in part by the blockade of endothelial integrin ,v,3. © 2001 Wiley-Liss, Inc. [source]

    Perineural meperidine blocks nerve conduction in a dose-related manner: a randomized double-blind study

    Background: Meperidine has been shown to exhibit a sensory block in peripheral nerves. However, its motor blockade ability is controversial. The aim of this study was to investigate, electroneurographically, the ability of meperidine to inhibit conduction in both sensory and motor fibres in the ulnar nerve. Materials and methods: The study was conducted in a double-blind, placebo-controlled fashion. Eighteen healthy volunteers were randomized into three groups (Saline, meperidine 1% and meperidine 2%). Three millilitre of the study solution was administered to the ulnar nerve perineurally at the level of the wrist by the guidance of a nerve stimulator. Sensory nerve action potential (SNAP) and compound motor action potential (CMAP) amplitudes were recorded. At least a 20% decrease in the initial response amplitude was accepted as a block. Results: The number of individuals with sensory and motor block with saline, meperidine 1% and meperidine 2% were 0/6, 6/6, 6/6 and 0/6, 5/6, 6/6, respectively (P<0.05). The maximum decrease in the median SNAP and CMAP amplitude values were 4.7% and 8.3% with saline; 38.5% and 46.4% with meperidine 1%; and 100% and 97.8% with meperidine 2%, respectively (P<0.05). Median values for the duration of sensory and motor block with meperidine 1% and meperidine 2% were 45, 52.5 and 30, 32.5 min, respectively. Conclusion: Meperidine blocks sensory and motor nerve conduction in a dose-related manner. [source]

    Characterization of nociceptin binding sites by novel peptide analogs and radioprobes

    S. Benyhe
    A number of new synthetic nociceptin ligands were studied in receptor binding and functional tests in rat brain membranes and in cloned systems. Ligand binding experiments were performed with three different radioprobes developed in our lab. The nociceptin derivatives exhibited high affinity in competition experiments. Receptor-mediated G-protein activation was determined in [35S]GTPgS binding assays. Among the new structures examined, Ac-RYYRIK-ol was found to be only a weak stimulator by itself, whereas this compound inhibited receptor-mediated G-protein activation. These data suggest that Ac-RYYRIK-ol is a high affinity peptide antagonist for the nociceptin receptor. Acknowledgements:, Supported by the Hungarian Scientific Research Fund OTKA T-035211, T-033078, T-030841, and the Ministry of Education, NKFP 1/027 Hungary. [source]

    RGS7 Is Palmitoylated and Exists as Biochemically Distinct Forms

    Jeremy J. Rose
    Abstract:Regulator of G protein signaling (RGS) proteins are GTPase-activating proteins that modulate neurotransmitter and G protein signaling. RGS7 and its binding partners G, and G,5 are enriched in brain, but biochemical mechanisms governing RGS7/G,/G,5 interactions and membrane association are poorly defined. We report that RGS7 exists as one cytosolic and three biochemically distinct membrane-bound fractions (salt-extractable, detergent-extractable, and detergent-insensitive) in brain. To define factors that determine RGS7 membrane attachment, we examined the biochemical properties of recombinant RGS7 and G,5 synthesized in Spodoptera frugiperda insect cells. We have found that membrane-bound but not cytosolic RGS7 is covalently modified by the fatty acid palmitate. G,5 is not palmitoylated. Both unmodified (cytosolic) and palmitoylated (membrane-derived) forms of RGS7, when complexed with G,5, are equally effective stimulators of G,o GTPase activity, suggesting that palmitoylation does not prevent RGS7/G,o interactions. The isolated core RGS domain of RGS7 selectively binds activated G,i/o in brain extracts and is an effective stimulator of both G,o and G,i1 GTPase activities in vitro. In contrast, the RGS7/G,5 complex selectively interacts with G,o only, suggesting that features outside the RGS domain and/or G,5 association dictate RGS7-G, interactions. These findings define previously unrecognized biochemical properties of RGS7, including the first demonstration that RGS7 is palmitoylated. [source]

    CYR61 (CCN1) Protein Expression during Fracture Healing in an Ovine Tibial Model and Its Relation to the Mechanical Fixation Stability

    Jasmin Lienau
    Abstract The formation of new blood vessels is a prerequisite for bone healing. CYR61 (CCN1), an extracellular matrix-associated signaling protein, is a potent stimulator of angiogenesis and mesenchymal stem cell expansion and differentiation. A recent study showed that CYR61 is expressed during fracture healing and suggested that CYR61 plays a significant role in cartilage and bone formation. The hypothesis of the present study was that decreased fixation stability, which leads to a delay in healing, would lead to reduced CYR61 protein expression in fracture callus. The aim of the study was to quantitatively analyze CYR61 protein expression, vascularization, and tissue differentiation in the osteotomy gap and relate to the mechanical fixation stability during the course of healing. A mid-shaft osteotomy of the tibia was performed in two groups of sheep and stabilized with either a rigid or semirigid external fixator, each allowing different amounts of interfragmentary movement. The sheep were sacrificed at 2, 3, 6, and 9 weeks postoperatively. The tibiae were tested biomechanically and histological sections from the callus were analyzed immunohistochemically with regard to CYR61 protein expression and vascularization. Expression of CYR61 protein was upregulated at the early phase of fracture healing (2 weeks), decreasing over the healing time. Decreased fixation stability was associated with a reduced upregulation of the CYR61 protein expression and a reduced vascularization at 2 weeks leading to a slower healing. The maximum cartilage callus fraction in both groups was reached at 3 weeks. However, the semirigid fixator group showed a significantly lower CYR61 immunoreactivity in cartilage than the rigid fixator group at this time point. The fraction of cartilage in the semirigid fixator group was not replaced by bone as quickly as in the rigid fixator group leading to an inferior histological and mechanical callus quality at 6 weeks and therefore to a slower healing. The results supply further evidence that CYR61 may serve as an important regulator of bone healing. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source]

    Sensitivity to ,-adrenoceptor agonists of adipocytes from rats treated with an aqueous extract of Croton cajucara Benth

    Dora Maria Grassi-Kassisse
    ABSTRACT Aqueous extracts of Croton cajucara bark are used in folk medicine to treat hepatic and gastrointestinal disorders and as a coadjuvant in weight-loss programs. We examined the effect of treating rats for 15 days with a 5% aqueous extract of C. cajucara on body weight and food intake. The epididymal adipose pads were removed and the lipolytic responses of isolated adipocytes to isoprenaline, noradrenaline (norepinephrine), BRL37344 and adrenaline (epinephrine) were analysed in the absence or presence of metoprolol or ICI118,551. Treated rats had a significantly lower weight gain than control rats, with no difference in food and liquid intake, epididymal fat-pad weight or basal glycerol release. The sensitivity of the lipolytic response to isoprenaline and adrenaline was significantly higher in adipocytes from treated rats. The sensitivity to noradrenaline or BRL37344 was unaltered. Metoprolol shifted the dose-response curves to noradrenaline to the right in adipocytes from control and treated rats; the dose-response curve to isoprenaline in adipocytes from control rats was also shifted to the right. In adipocytes from treated rats, the dose-response curve to isoprenaline was unaltered by metoprolol but was shifted to the right by ICI118,551, a ,2 -adrenoceptor antagonist. We conclude that in adipocytes from treated rats there is an increase in the lipolytic response to non-selective agonists (isoprenaline and adrenaline) mediated by ,2 -adrenoceptors, with no alteration in the responses mediated by ,1 -adrenoceptors (noradrenaline) or ,3 -adrenoceptors (BRL37344). This effect could increase the role of adrenaline as an endogenous stimulator of lipolysis. [source]

    Cervical epidural analgesia via a thoracic approach using nerve-stimulation guidance in adult patients undergoing total shoulder replacement surgery

    B. C. H. Tsui
    Background:, Continuous cervical epidural anesthesia can provide excellent peri- and post-operative analgesia, although several factors prevent its widespread use. Advancing catheters from thoracic levels to the cervical region may circumvent these barriers, provided they are accurately positioned. We hypothesize that guiding catheters from thoracic to cervical regions using low-current epidural stimulation will have a high success rate and enable excellent analgesia in adults undergoing total shoulder arthroplasty. Methods:, After Institutional Review Board approval, adult patients were studied consecutively. A 17-G Tuohy needle was inserted into the thoracic epidural space using a right paramedian approach with loss of resistance. A 20-G styletted epidural catheter, with an attached nerve stimulator, was primed with saline and a 1,10 mA current was applied as it advanced in a cephalad direction towards the cervical spine. Muscle twitch responses were observed and post-operative X-ray confirmed final placement. After a test dose, an infusion (2,8 ml/h) of ropivacaine 2 mg/ml and morphine 0.05 mg/ml (or equivalent) was initiated. Verbal analog pain scale scores were collected over 72 h. Results:, Cervical epidural anesthesia was performed on 10 patients. Average current required to elicit a motor response was 4.8 ± 2.0mA. Post-operative X-ray of catheter positions confirmed all catheter tips reached the desired region (C4,7). The technical success rate for catheter placement was 100% and excellent pain control was achieved. Catheters were positioned two to the left, four to the right and four to the midline. Conclusion:, This epidural technique provided highly effective post-operative analgesia in a patient group that traditionally experiences severe post-operative pain and can benefit from early mobilization. [source]

    Erythromycin prior to endoscopy for acute upper gastrointestinal haemorrhage: a cost-effectiveness analysis

    Summary Background, Erythromycin is a potent stimulator of gastrointestinal motility. Recent studies have examined the use of intravenous erythromycin to clear the stomach of blood before oesophago-gastroduodenoscopy (EGD) for acute upper gastrointestinal haemorrhage (UGIH). These studies have shown clinical effectiveness. Aim, To evaluate the cost-effectiveness of this intervention. Methods, We sought to determine the cost-effectiveness of erythromycin before EGD from the payer's perspective. We found three relevant studies of erythromycin and used these data for the analysis. We obtained costs for intravenous erythromycin and charges for peptic ulcer hospitalization, EGD, surgery, and angiographic embolization. Complication rates were also incorporated from the literature. We implemented a model of health-related quality of life to measure the impact of the intervention. We created a decision-analysis tree and performed a probabilistic sensitivity analysis. Results, A strategy of erythromycin prior to EGD resulted in a cost-effective outcome in a majority of trials using willingness-to-pay figures of $0, $50 000 and $100 000 (US) per quality-adjusted life-year (QALY). Conclusion, Because of the implications for cost saving and increase in QALY, we would recommend giving erythromycin prior to EGD for UGIH. [source]

    RNA interference targeting the platelet-derived growth factor receptor , subunit ameliorates experimental hepatic fibrosis in rats

    LIVER INTERNATIONAL, Issue 10 2008
    Si-Wen Chen
    Abstract Background/Aims: Platelet-derived growth factor (PDGF) is the strongest stimulator of the proliferation of hepatic stellate cells (HSCs). PDGF receptor , subunit (PDGFR-,) is acquired on HSCs proliferation induced by PDGF. In this study, we aim to investigate the effect of PDGFR-, small interference RNA (siRNA) on experimental hepatic fibrosis. Methods: We constructed a PDGFR-, siRNA expression plasmid and investigated its effect on the activation of HSCs. Bromodeoxyuridine incorporation was performed to investigate the effect of PDGFR-, siRNA on HSCs proliferation. A hydrodynamics-based transfection method was used to deliver PDGFR-, siRNA to rats with hepatic fibrosis. The distribution of transgenes in the liver was observed by immunofluorescence. The antifibrogenic effect of PDGFR-, siRNA was investigated pathologically. Results: Platelet-derived growth factor receptor-, subunit siRNA could significantly downregulate PDGFR-, expression, suppress HSCs activation, block the mitogen-activated protein kinase signalling pathway and inhibit HSCs proliferation in vitro. PDGFR-, siRNA expression plasmid could be delivered into activated HSCs by the hydrodynamics-based transfection method, and remarkably improve the liver function of the rat model induced by dimethylnitrosamine and bile duct ligation. Furthermore, the progression of fibrosis in the liver was significantly suppressed by PDGFR-, siRNA in both animal models. Conclusions: Platelet-derived growth factor receptor-, subunit siRNA may be presented as an effective antifibrogenic gene therapeutic method for hepatic fibrosis. [source]