Dysregulation of low-voltage-activated calcium channels (CaV3.1-CaV3.3) underlies diseases including chronic pain, autism, and hypertension. As a major determinant of protein half-life, the ubiquitin-proteasome system (UPS) may not only cause abnormal CaV3 expression but also be targeted to control channel levels for therapy. There are >600 E3 ubiquitin ligases that catalyse the final step in ubiquitination. A crucial aspect of harnessing the UPS is knowing which E3 ligases regulate a given substrate, and whether their actions are redundant. We report that CaV3.1 and CaV3.2 are distinctively regulated by two NEDD4 family E3 ligases – NEDD4L and Smurf1. Reconstituted CaV3.1 currents were robustly suppressed by Smurf1 but not NEDD4L, whereas CaV3.2 was inhibited by both NEDD4L and Smurf1, concomitant with diminished channel surface density and expression. FRET experiments revealed NEDD4L and Smurf1 interact with distinct loci in CaV3.1 and CaV3.2. Nanobody-mediated targeting of NEDD4L or Smurf1, but not WWP1, HECT domains to CaV3.1 and CaV3.2 strongly suppressed currents through both channels. shRNA knockdown of either NEDD4L or Smurf1 in dorsal root ganglion (DRG) neurons substantially increased both low-voltage and high-voltage-activated calcium channel currents. The results reveal non-redundant regulation of CaV3 channels by NEDD4L and Smurf1; introduce Smurf1 as a potent determinant of ion channel expression; suggest a new mechanism for CaV3.2 up-regulation in chronic pain; and advance leveraging the UPS to control CaV3 expression for therapy.

No description available.

Thesis (M. Tech.) -- Central University of Technology, Free State, 2008 / The aim of the study was to determine radiation dose levels around the theatre table, on either side of the C-Arm, in order to establish if the radiation dose received by staff during back pain procedures fell within the limits set by the International Commission of Radiological Protection (ICRP). The question that arose from this goal was whether the stance of staff, in relation to the x-ray tube side of the C-Arm, influenced radiation dose levels. In order to apply the ALARA principle, the possibility of lowering the radiation dose in the neurological theatre was explored. The measurement methodology of the study was twofold: measurements were executed by means of TLD meters, as well as with an ionisation chamber. TLD meters were placed on the patient, the neurosurgeon and the radiographer during back pain procedures, and, more specifically, during fluoroscopy, to record the doses with the Image Intensifier (II) above the table as well as with the x-ray tube above the table, at the pelvis and the chest height of the staff. Ionisation chamber measurements were recorded in 25cm intervals around the theatre table with a phantom and the C-Arm positioned in the PA, oblique and lateral positions at 110cm and 133cm heights from the floor. The TLD results indicated that, when compared to the Image Intensifier side, the radiation dose was higher on the x-ray tube side of the C-Arm. The radiation dose was higher at the height closest to the x-ray source. The radiation dose received by the patient was higher with the x-ray tube positioned above the table (PA). The radiation dose to the surgeon’s hand and body was higher with the x-ray tube positioned above the table (PA). Radiation dose levels with the x-ray tube above the table during back pain procedures in the current theatre exceeded the occupational annual recommendation of 500mSv to the neurosurgeons hands, as recommended by the ICRP. The opposite is true with the II positioned above the table. The research question was answered positively in that the x-ray tube under couch orientation has the potential to limit dose levels during back pain procedures. The measurement values resulted in a proposed protocol in terms of positioning of staff and orientation of the C-Arm in order to apply the ALARA principle during back pain procedures. Constant revision of protocols is the responsibility of the radiographer in order to guarantee that the ALARA principle is implemented in every unique situation.

Dissertation submitted in fulfillment of the requirements for the Degree of Master of Technology: Emergency Medical Care, Durban University of Technology, 2012. / Background In the emergency setting, the onus is on the individual practitioner’s ability to make critical decisions at critical moments in order to provide the best level of care to their patient. In order to ensure that these decisions fall in line with the best interests of the patient, the South African paramedic requires a better understanding of how to arrive at such a decision; they need to understand the clinical decision making process. This study focused on South African paramedic clinical decision making with specific reference to acute traumatic pain management, with the aim of determining the factors which influence South African paramedic clinical decision making by revealing the current method of pain management employed by South African paramedics, how they view the priority of pain management in the continuum of care and if there were any context specific factors influencing their clinical decision making. Methods A mixed method design was used to determine the factors contributing to the clinical decision making process of South African paramedics in the acute pain management of patients with acute traumatic pain. A mixture of qualitative and quantitative approaches was utilized by means of a research questionnaire as well as in-depth interviews. The questionnaires were targeted at all South African paramedics while the in-depth interviews were conducted with five participants who had been purposefully selected from the questionnaire respondents. The data analysis was conducted in a descriptive manner in order to inform the explanatory nature of the answers to the research questions and objective. Results The results provided insight into the current methods and clinical decision making processes employed by South African paramedics in the management of patients’ experiencing acute traumatic pain. The study determined that the South African paramedic’s clinical decision making process involves three key phases in the acute traumatic pain management setting, the assessment phase, the initiation/pain management phase and the conclusion/re-evaluation phase, with each phase utilizing different decision making models, the intuitive/humanist model, the hypothetico- deductive model and a model which combined both of the aforementioned models. In addition to this, numerous factors such as the provision of care in order to facilitate further management and transportation to an appropriate facility, which influenced clinical decision making, were identified. Amongst South African paramedics, pain management was identified as coming second only to the interventions required to manage immediately life threatening conditions in terms of the prioritization of treatment. Recommendations A variety of recommendations which included the need to further the development of clinical decision making and pain management through research and education as well as considerations for investigation into the potential expansion of South African paramedic scope of practice in the pain management environment were made.

Opioider har blivit en vanligare behandlingsmetod för patienter med långvarig smärta som bidrar till att patienten upplever adekvat smärtlindring. Smärtlindringen kan dock leda till att patienter utsätts för opioidinducerade risker som leder till att patienten inte erhåller adekvat smärtlindring. Syftet med studien var att belysa patienters upplevelser av att behandlas med opioider vid långvarig smärta. Litteraturstudien utgår från en induktiv ansats och resultatet grundas på 14 vetenskapliga artiklar, varav sju artiklar är kvalitativa samt sju är kvantitativa. En innehållsanalys användes vilket resulterade i tre olika teman: Det professionella och sociala stödet, Inverkan på kropp och själ samt Vilja till att bemästra opioidbehandlingen. Resultatet visade både positiva och negativa upplevelser bland patienter med långvarig smärta som behandlas med opioider. Patienterna upplevde det professionella mötet som särskilt betydelsefullt då det ingav hopp och stöd. Patienter kunde däremot också uppleva förutfattade meningar samt negativa attityder vilket bidrog till bristfällig omvårdnad för patienterna. Studien föreslår att sjuksköterskor är i behov av utbildning och kunskap angående opioider och dess inverkan på kroppen för att bidra med god patientutbildning samt god omvårdnad. / Opioids have become a common method of treatment for patients with chronic pain that contribute to adequate pain relif. Pain relief can lead to patients being exposed to opioid-induced risks that causes inadequate pain relief for the patients. The aim of the study was to highlight patients experiences of being treated with opioids for chronic pain. The literature review is based on a inductive approach and the results are based on 14 scientific articles, including seven qualitative articles and seven quantitative articles. A content analysis of the article was used which resulted in three different themes: The professional and social support, Impact on the body and mind and Will to overcome opioid-therapy. The result showed both positive and negative experiences among patients with chronic pain treated with opioids. Patients experienced the professional meeting as particularly significant because it gave them hope and support. Patients could however also experience prejudice and negative attitudes which contributed to inadequate care for the patients. The study suggests that nurses are in need of education and knowledge about opioids and their impact on the body to contribute with good patient education and good nursing care.

No description available.

O câncer é a maior causa de morbidade e mortalidade em animais idosos de companhia, sendo a dor o principal sintoma relatado no homem. Objetivou-se, neste estudo, avaliar o emprego do tramadol para analgesia em cães com dor oncológica. Foram avaliados cães com câncer no período de agosto de 2004 a março de 2006, encaminhados ao Grupo de Dor do Serviço de Anestesia. Incluiu-se no estudo cães que permaneceram no mínimo 15 dias em tratamento e que, no momento de instituição da terapêutica com o tramadol, apresentaram dor igual ou maior que 4, de acordo com Escala Numérica Verbal (ENV) quando já medicados com dipirona associada ou não a antiinflamatórios não esteroidais ou esteroidais há mais de 10 (dez) dias. Avaliou-se a dor com a ENV e o escore de qualidade de vida (QV) através de escala validada para cães (Yazbek; Fantoni, 2000). Foram avaliados para o estudo 130 animais com câncer, 53 machos e 77 fêmeas, dos quais 37 obedeceram aos critérios de inclusão para análise da terapia analgésica. De acordo com a avaliação dos proprietários, a média de dor dos animais avaliados pela da ENV no momento de instituição da terapêutica com o tramadol foi de 6,11 ± 1,81 e o escore de qualidade de vida foi 21,95 ± 5,96. No primeiro retomo velificou-se melhora da dor em 31 (83,78%) animais. Neste momento foi realizada adequação da dose do tramadol, considerando-se a intensidade da dor em 20 (54,05%) dos 37 cães era superior a 4. No segundo retomo 34 (91,89%) dos animais apresentaram alívio da dor em relação à consulta inicial, sendo que 28 (75,68%) destes obtiveram ENV inferior a 4. A dose inicial preconizada do tramadol foi de 2mg/Kg a cada 8 horas, por via oral, sendo esta dose reajustada no retomo caso o valor de ENV fosse maior que 4. Classificando a eficácia do tratamento realizado com o tramadol em três categorias: alívio da dor (ENVinicial > ENVfinal e ENVfinal < 4), melhora insatisfatória (ENVinicial > ENVfinal e ENVfinal > 4) e ausência de melhora (ENVinicial &le; ENVfinal) pode-se afirmar que no primeiro retomo 83,78% e 78,28% dos pacientes, na opinião de proprietário e pesquisador respectivamente, experimentaram alguma melhora da dor. Seguindo esta mesma classificação observou-se que, no segundo retomo após acerto da dose do tramadol, o alívio da dor foi obtido em 28 (75,68%) animais na opinião de proprietário e pesquisador e melhora insatisfatória em 6 (16,21%) e 7 (18,91%) pacientes, de acordo com o proprietário e pesquisador respectivamente. Quando comparados os grupos separadamente verifica-se que o grupo DAINET (dipirona, AINE, tramadol) apresentou significante alívio da dor em relação aos primeiro retorno e a avaliação final, já os grupos DT (dipirona, tramadol) e DET (dipirona, esteróide, tramadol) apresentaram alívio da dor apenas em relação a avaliação final. Com base no alívio da dor e no aumento da qualidade de vida, pode-se concluir que o tramadol foi eficiente no tratamento da dor de grau moderada à intensa em cães portadores de câncer. / Cancer is the main cause of morbidity and mortality in companion aged dogs, being pain the principal symptom described in humans. This study aimed to evaluate the use of tramadol for analgesia in dogs with oncologic pain. Between august 2004 and marc 2006, dogs with cancer referred to the Pain Group of the Anesthesia Service were evaluated. In this study , dogs with at least fifteen days of treatment were included and that at the moment at tramadol administration, presented pain equal or above 4 according the Visual Analogue Scale (VAS) when treated with dypirona associated our not to non-esteroidal anti-inflammatory analgesics or steroidal for more than 10 days. Pain evaluated with the VAS and the quality of life (QV) score validated for dogs (Yazbek; Fantoni, 2000) were used. One hundred and thirty seven dogs with cancer were evaluated, but only 37 could be included the evaluation of analgesic therapy. According to the owner of the animals by means of the VAS at the begging of tramadol was 6,11 ± 1,81 and the QV score was 21,95 ± 5,96. At the first return, an improvement in pain was verified in 31 animals (83,78%). In this moment, adequacy of tramadol dose was performed, since the intensity of pain was above 4 in 20 (54,05%) animals. At the second returns 34 (91,89%) of the animals presented pain relief in relation to the first visit, being that 28 (75,68%) of the animal presented a VAS bellow 4 the initial dose o tramadol was 2mg/Kg each 8 hours orally, and the dose was readjusted in the return who the animal presented VAS above 4. Efficacy of treatment was classified in the three steps pain relief: successful pain relief (initial VAS > final VAS and final VAS < 4), unsuccessful pain relief (initial VAS > final VAS and final VAS > 4) and no pain relief (initial VAS &le; final VAS). It could be inferred that at the first return 83,78% and 78,28% of patients regarding owner and researcher opinion respectively obtained some pain relief. Following this some classification, it was observed that at the second return after adjusting the tramadol dosage, pain relieve was achieved in 28 (75,68%) of the animals the according to the owner and researcher and that an unsuccessful relief in 6 (16,21%) and 7 (18,91%) of patients respectively. When the groups were compared separately it was verified that the group DAINET (dypirona, AINE and tramadol) showed a significant pain relief in relation to the final evaluation, whereas the other two groups (DT - dypirona plus tramadol - and DET - dypirona, steroidal anti-inflammatory analgesic and tramadol) presented pain relief only in relation to the final evaluation. Based on the results of pain relief and QV it could be concluded that tramadol was efficient regarding the treatment of moderate to severe pain in dogs with cancer.

Chan, Hoi Sze Gloria. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 204-241). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract and appendixes also in Chinese.

Thoracic paravertebral block (TPVB) consists of an injection of local anaesthetic alongside the thoracic vertebra close to where the spinal nerves emerge from the intervertebral foramen. Clinically TPVB can be accomplished either as a single-injection or as a multiple-injection. It can also be used as a continuous paravertebral infusion through an indwelling catheter for continuous pain relief. However compared to an epidural block, TPVB is less well understood and not commonly used for anaesthesia and or analgesia in anaesthetic practice. I hypothesized that TPVB is effective for producing unilateral segmental thoracic anaesthesia and managing pain of unilateral origin from the thorax. / The objective of this thesis was to develop the technique of TPVB so that it becomes a useful technique for anaesthesia and pain management. So to test my hypothesis a series of clinical studies were performed on 416 patients (396 adults and 20 young infants), presenting for anaesthesia and or acute pain management, to evaluate various aspects of TPVB, namely; clinical application, anatomy of the thoracic paravertebral space, technique and safety, and pharmacology of local anaesthetic after TPVB. Also included are 9 published case reports and letters-to-editor (Appendix 1-9) based on my research that have provided new insights into the mechanism and applications of TPVB. The following section summarizes my research... / Karmakar, Manoj Kumar. / Thesis (M.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 270-285). / Appendix includes Chinese. / ABSTRACT --- p.v / PREFACE --- p.xxvii / STATEMENT OF WORK --- p.xxviii / ACKNOWLEDGEMENTS --- p.xxix / PUBLICATIONS AND PRESENTATIONS --- p.xxxii / LIST OF ABBREVIATIONS --- p.xxxviii / LIST OF TABLES --- p.xli / LIST OF FIGURES --- p.xliii / Chapter Part 1. --- Introduction --- p.1 / Chapter Chapter 1. --- Objective and Plan of Research --- p.2 / Chapter Chapter 2. --- Thoracic Paravertebral Block A Review of the Literature. --- p.7 / Chapter 2.1. --- Introduction --- p.7 / Chapter 2.2. --- History --- p.7 / Chapter 2.3. --- Anatomy: --- p.9 / Chapter 2.4. --- Techniques --- p.17 / Chapter 2.4.1. --- Anatomical Landmark Based Techniques --- p.20 / Chapter 2.4.1.1. --- Loss-of-resistance Technique --- p.20 / Chapter 2.4.1.2. --- Advancing the Block Needle by a pre-determined Distance --- p.23 / Chapter 2.4.1.3. --- Other Landmark Based Techniques --- p.24 / Chapter 2.4.2. --- Fluoroscopic Guidance or Injection of Radiopaque Contrast medium --- p.24 / Chapter 2.4.3. --- Peripheral Nerve Stimulation --- p.25 / Chapter 2.4.4. --- Pressure Measurement Technique --- p.26 / Chapter 2.5. --- Thoracic Paravertebral Catheter Placement --- p.27 / Chapter 2.6. --- Ultrasound Guided Thoracic Paravertebral Block --- p.32 / Chapter 2.6.1. --- Two Dimensional (2D) Sonoanatomy of the Thoracic Paravertebral Region --- p.32 / Chapter 2.6.1.1. --- Basic Considerations --- p.32 / Chapter 2.6.1.2. --- Transverse Scan of the Thoracic Paravertebral Region --- p.33 / Chapter 2.6.1.3. --- Sagittal Scan of the Thoracic Paravertebral Region --- p.42 / Chapter 2.6.2. --- Three Dimensional (3D) Sonoanatomy of the Thoracic Paravertebral Region --- p.46 / Chapter 2.6.3. --- Ultrasound Guided Thoracic Paravertebral Block - Techniques --- p.49 / Chapter 2.6.3.1. --- Transverse scan with short axis needle insertion (Technique 1) --- p.54 / Chapter 2.6.3.2. --- Paramedian Sagittal scan with in-plane needle insertion (Technique 2) --- p.56 / Chapter 2.6.3.3. --- Transverse scan with in-plane needle insertion or the Intercostal approach to the TPVS (Technique 3) --- p.58 / Chapter 2.7. --- Mechanism and Spread of Anaesthesia --- p.58 / Chapter 2.8. --- Indications --- p.65 / Chapter 2.9. --- Contraindications --- p.65 / Chapter 2.10. --- Drugs Used and Dosage --- p.68 / Chapter 2.11. --- Pharmacokinetic Considerations --- p.70 / Chapter 2.12. --- Failure Rate and Complications --- p.72 / Chapter 2.13. --- Clinical Applications of Thoracic Paravertebral Block --- p.76 / Chapter 2.13.1. --- Pain Relief after Thoracic Surgery --- p.76 / Chapter 2.13.2. --- Pain Relief after Multiple Fractured Ribs --- p.78 / Chapter 2.13.3. --- Anaesthesia and Analgesia for Breast Surgery --- p.80 / Chapter 2.13.4. --- Thoracic Paravertebral Block and Chronic Pain after Breast Cancer Surgery --- p.84 / Chapter 2.13.5. --- Thoracic Paravertebral Block and Cancer Recurrence after Breast Cancer Surgery --- p.85 / Chapter 2.13.6. --- Anaesthesia and Analgesia for Inguinal Herniorrhaphy --- p.87 / Chapter 2.13.7. --- Pain Relief after Cholecystectomy and Renal Surgery --- p.90 / Chapter 2.13.8. --- Anaesthesia and Analgesia for Liver and Biliary Tract Surgery --- p.91 / Chapter 2.13.9. --- Analgesia after Cardiac Surgery --- p.92 / Chapter 2.13.10. --- Thoracic Paravertebral Block and Chronic Pain Management --- p.94 / Chapter 2.13.11. --- Bilateral Thoracic Paravertebral Block --- p.94 / Chapter 2.13.12. --- Miscellaneous Applications --- p.95 / Chapter Part 2. --- Studies Evaluating the Efficacy of Thoracic Paravertebral Block in Adults. --- p.96 / Chapter Chapter 3. --- Prospective Randomized Evaluation of the Effects of Combining a Single-injection Thoracic Paravertebral Block with General Anesthesia in Patients Undergoing Modified Radical Mastectomy. --- p.97 / Chapter Chapter 4. --- Continuous Thoracic Paravertebral Infusion of Bupivacaine for Postthoracotomy Analgesia A Prospective, Randomized, Double Blind, Controlled Trial. --- p.120 / Chapter Chapter 5. --- Continuous Thoracic Paravertebral Infusion of Bupivacaine for Pain Management in Patients with Multiple Fractured Ribs. --- p.137 / Chapter Chapter 6. --- Thoracic Paravertebral Block and Its Effects on Chronic Pain and Health-related Quality of Life after Modified Radical Mastectomy. --- p.154 / Chapter Chapter 7. --- Right Thoracic Paravertebral Anaesthesia for Percutaneous Radiofrequency Ablation of Liver Tumours. --- p.186 / Chapter Part 3. --- Studies Evaluating The Efficacy Of Thoracic Paravertebral Block In Children. --- p.198 / Chapter Chapter 8. --- Continuous Extrapleural Paravertebral Infusion of Bupivacaine for Postthoracotomy Analgesia in Young Infants. --- p.199 / Chapter Part 4. --- Studies Evaluating The Anatomy Relevant For Thoracic Paravertebral Block. --- p.213 / Chapter Chapter 9. --- Thoracic Paravertebral Sonography - A Quantitative Evaluation of the Paramedian Sagittal Window for Visualizing the Anatomy Relevant for Thoracic Paravertebral Block. --- p.214 / Chapter Chapter 10. --- Volumetric 3D Ultrasound Imaging of the Anatomy Relevant for Thoracic Paravertebral Block. --- p.228 / Chapter Part 5. --- Pharmacokinetics of Ropivacaine after Thoracic Paravertebral Block. --- p.242 / Chapter Chapter 11. --- Arterial and Venous Pharmacokinetics of Ropivacaine With and Without Epinephrine after Thoracic Paravertebral Block. --- p.243 / Chapter Part 6. --- Summary and Conclusions --- p.266 / Chapter Chapter 12. --- Summary and Conclusions --- p.266 / Chapter Part 7. --- Bibliography --- p.270 / Chapter Part 8. --- Appendix --- p.296 / Chapter A. --- Published Case Reports and Letters-to-editor. --- p.297 / Chapter Appendix: 1.0. --- Variability of a Thoracic Paravertebral Block. Are we ignoring the endothoracic fascia? (Published Commentary) --- p.297 / Chapter Appendix: 2.0. --- Ipsilateral Thoraco-lumbar Anaesthesia and Paravertebral Spread after Low Thoracic Paravertebral Injection. (Published Case Report) --- p.301 / Chapter Appendix: 3.0. --- The Use of a Nerve Stimulator for Thoracic Paravertebral Block Reply. (Published Letter-to-editor) --- p.310 / Chapter Appendix: 4.0. --- Bilateral Continuous Paravertebral Block Used for Postoperative analgesia in an Infant having Bilateral Thoracotomy. (Published Case Report) --- p.312 / Chapter Appendix: 5.0. --- Thoracic Paravertebral Block: Radiological evidence of Contralateral Spread Anterior to the Vertebral Bodies. (Published Case Report) --- p.317 / Chapter Appendix: 6.0. --- Lymphatic Drainage of the Thoracic Paravertebral Space A Reply. (Published Letter-to-editor) --- p.325 / Chapter Appendix: 7.0. --- Thoracic Paravertebral Block for Management of Pain Associated with Multiple Fractured Ribs in Patients with Concomitant lumbar Spinal Trauma. (Published Case Report) --- p.328 / Chapter Appendix: 8.0. --- Right Thoracic Paravertebral Analgesia for Hepatectomy. (Published Case Report) --- p.340 / Chapter Appendix: 9.0. --- Resolution of ST-segment Depression after High Thoracic Paravertebral Block during General Anesthesia. (Published Case Report) --- p.348 / Chapter B. --- Medical Outcomes Study 36-Item Short-Form Questionnaire (SF-36) - Appendix 10. --- p.353 / Chapter C. --- Hospital Anxiety and Depression Scale - Appendix 11. --- p.362 / Chapter D. --- Postoperative Telephone Follow Up Questionnaire: Appendix 12. --- p.364

published_or_final_version / Anaesthesiology / Master / Doctor of Medicine