by Andy Cheng Shu Kei. / Year shown on spine: 1997. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (leaves [165-175]). / acknowledgements / abstract / Chapter chapter one --- introduction / Chapter 1.1 --- JUSTIFICATION OF RESEARCH --- p.1 / Chapter 1.2 --- STRUCTURE OF THESIS --- p.4 / Chapter chapter two --- literature review / Chapter 2.1 --- ANATOMY OF DIGITAL NERVE --- p.6 / Chapter 2.2 --- FACTORS AFFECTING RESULTS OF SENSIBILITY RECOVERY --- p.10 / Chapter 2.3 --- NEUROPHYSIOLOGY OF NERVE FIBRE / MECHANORECEPTORS --- p.16 / Chapter 2.4 --- NEUROPHYSIOLOGY OF TACTILE STIMULATION --- p.20 / Chapter 2.5 --- SENSIBILITY TESTING FOR FUNCTIONAL SENSIBILITY --- p.26 / Chapter 2.5.1 --- SEMMES-WEINSTEIN MONOFILAMENT / Chapter 2.5.2 --- CONSTANT TWO-POINT DISCRIMINATION / Chapter 2.5.3 --- MOVING TWO-POINT DISCRIMINATION / Chapter 2.5.4 --- SELF EVALUATION / Chapter chapter three --- retrospective study of the sensibility recovery of peripheral nerve injuries / Chapter 3.1 --- INTRODUCTION --- p.38 / Chapter 3.2 --- OBJECTIVES --- p.38 / Chapter 3.3 --- METHODOLOGY --- p.38 / Chapter 3.4 --- RESULTS --- p.42 / Chapter 3.5 --- DISCUSSION AND IMPLICATION --- p.43 / Chapter chapter four --- longitudinal study of the sensibility recovery of digital nerve injuries / Chapter 4.1 --- INTRODUCTION --- p.45 / Chapter 4.2 --- OBJECTIVES --- p.45 / Chapter 4.3 --- METHODOLOGY --- p.46 / Chapter 4.4 --- RESULTS --- p.50 / Chapter 4.5 --- DISCUSSION AND IMPLICATION --- p.57 / Chapter chapter five --- "functional sensibility - normative values and correlation with age, sex,occupation and skin hardness in local chinese population" / Chapter 5.1 --- INTRODUCTION --- p.59 / Chapter 5.2 --- OBJECTIVES --- p.60 / Chapter 5.3 --- METHODOLOGY --- p.60 / Chapter 5.4 --- RESULTS --- p.64 / Chapter 5.5 --- DISCUSSION AND IMPLICATION --- p.84 / Chapter chapter six --- prospective randomised study of early tactile stimulation in digital nerve injuries / Chapter 6.1 --- INTRODUCTION --- p.87 / Chapter 6.2 --- OBJECTIVES --- p.88 / Chapter 6.3 --- METHODOLOGY --- p.89 / Chapter 6.4 --- RESULTS --- p.95 / Chapter 6.5 --- DISCUSSION AND IMPLICATION --- p.115 / Chapter chapter seven --- conclusions and recommendations / Chapter 7.1 --- CONCLUSIONS --- p.121 / Chapter 7.2 --- RECOMMENDATIONS --- p.125 / appendices / Chapter I --- INSTRUCTION MANUAL FOR ASSESSING FUNCTIONAL SENSIBILITY --- p.126 / Chapter II --- CLASSIFICATION OF LEVEL OF FINGER DEXTERITY IN WORK --- p.129 / Chapter III --- RANDOM TABLE IN MAIN STUDY --- p.132 / Chapter IV --- SCHEMATIC DIAGRAM OF INTERNAL STRUCTURE OF TACTILE STIMULATOR --- p.133 / Chapter V --- CONSENT FORM --- p.134 / Chapter VI --- ASSESSMENT FORM IN RETROSPECTIVE STUDY --- p.135 / Chapter VII --- ASSESSMENT FORM IN LONGITUDINAL AND MAIN STUDY(LEFT HAND) --- p.137 / Chapter VIII --- ASSESSMENT FORM IN LONGITUDINAL AND MAIN STUDY(RIGHT HAND) --- p.138 / Chapter IX --- ASSESSMENT FORM IN CORRELATIONAL STUDY --- p.139 / Chapter X --- INTER-RATER VARIATION IN ASSESSING SENSIBILITY RECOVERY IN LONGITUDINAL STUDY --- p.140 / Chapter XI --- NORMATIVE VALUES OF FUNCTIONAL SENSIBILITY AND SKIN HARDNESS --- p.142 / Chapter XII --- INTER-RATER VARIATION IN ASSESSING SENSIBILITY RECOVERY IN MAIN STUDY --- p.162 / references

CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel Superior / Oxaliplatina (OXL) à um composto de platina de terceira geraÃÃo com potente atividade citotÃxica contra vÃrios tipos de cÃncer, possuindo um efeito colateral de difÃcil tratamento, uma severa neuropatia perifÃrica. Estudos sugerem que o oxalato, metabÃlito da OXL, està envolvido no desenvolvimento dessa neuropatia sensitiva perifÃrica (NSP); de modo que foi publicada a sÃntese de um anÃlogo (LLC-1402) da OXL, livre de oxalato, tendo propriedades antitumorais (LIU et al., 2013). O objetivo do trabalho à estudar o papel do oxalato na neuropatia induzida por OXL em camundongos, comparando a OXL com LLC-1402. A NSP foi induzida por 2 injeÃÃes (iv.) por semana de OXL (2 mg/kg), em camundongos machos Swiss, durante 4  semanas, totalizando 9 injeÃÃes. LLC-1402 (7, 14 e 28 mg/kg) foi administrado (iv.) seguindo o mesmo esquema. Foram realizados testes nociceptivos (Von Frey eletrÃnico e TIC), semanalmente. Depois, foi escolhida a dose de 14 mg/kg do LLC-1402 para fazer um outro experimento, no qual foi acrescentada a injeÃÃo ip. de oxalato (1,7 mg/kg). No 28 dia, foi feita coleta de sangue para contagem total de leucÃcitos e dosagens bioquÃmicas. Nos 28 e 56 dias, foi feita a coleta de medula espinhal e GRD para imunofluorescÃncia para ATF-3, c-FOS, iNOS e NeuN. Os resultados mostraram que a OXL e o LLC-1402 foram capazes de diminuir o limiar de retirada da pata e o tempo de retirada da cauda significativamente (p<0,05), comparado ao grupo controle. A injeÃÃo de LLC-1402 junto com oxalato e somente oxalato tambÃm foi capaz de reduzir o limiar de retirada da pata e o tempo de retirada da cauda. Os grupos tratados com OXL, LLC-1402 e oxalato mostraram uma reduÃÃo significativa da contagem total de leucÃcitos. Para as dosagens bioquÃmicas (TGO, TGP, ureia, creatinina), nÃo houve diferenÃa estatÃstica entre os grupos. Houve um aumento da imunoexpressÃo de c-Fos no GRD nos grupos tratados com OXL, LLC-1402 e LLC-1402 junto com oxalato nos 28 e 56 dias, e somente oxalato no 28 dia. Foi observado esse aumento no corno dorsal da medula espinhal no 28 dia em todos os grupos tratados. Foi observado um aumento da imunoexpressÃo de ATF-3, no GRD e corno dorsal da medula espinhal, em todos os grupos tratados, nos 28 e 56 dias. NÃo houve diferenÃa significativa entre os grupos no GRD nem medula espinhal na imunoexpressÃo de iNOS no 56 dia; jÃ, no 28 dia, houve um aumento da imunoexpressÃo de iNOS no GRD. Os resultados mostraram que o oxalato pode estar envolvido parcialmente na NSP induzida por OXL. / Oxaliplatin (OXL) is a third generation platinum compound with potent cytotoxic activity against several types of cancers, having a side effect is difficult to treat, a severe peripheral neuropathy. Studies suggest that oxalate, OXL metabolite, is involved in the development of peripheral sensory neuropathy (PSN); so that was published the synthesis of an OXL analogue (LLC-1402), oxalate free, which has antitumor properties (LIU et al., 2013). The objective of this research is to study the role of oxalate in OXL induced neuropathy in mice, comparing OXL with LLC-1402. The PSN was induced by two injections (iv.) OXL (2 mg/ kg) per week, in male Swiss mice, for 4  weeks, totaling 9 injections. LLC-1402 (7, 14 and 28 mg / kg) was administered (iv.) following the same scheme. Nociceptive tests were performed (electronic von Frey and tail immersion test) weekly. After, it was chosen dose of 14 mg / kg of the LLC-1402 to perform another experiment, in which was added oxalate injection (1.7 mg/kg). In the 28th day, it was made blood collection for total leukocyte count and biochemical measurement. In the 28th and 56th days, spinal cord and DRG were removed for immunofluorescence for ATF-3, c-FOS, iNOS and NeuN. The results showed that both OXL and LLC-1402 were able to decrease the paw withdrawal threshold and tail withdrawal time significantly (p<0.05) compared to the control group. The injection of LLC-1402 together with oxalate and only oxalate was also able to reduce the paw withdrawal threshold and the tail withdrawal time. Moreover, all groups treated with OXL, LLC-1402 and oxalate showed a significant reduction in the total leukocyte count. The biochemical measurement (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, urea, creatinine) showed no statistical difference between the groups. The results also showed increased c-Fos immunoexpression in GRD in groups treated with OXL, LLC-1402 and LLC-1402 together with oxalate in the 28 and 56 days, and only oxalate the 28th day. This increase was observed in the dorsal horn of the spinal cord at 28th day in all the treated groups. It was not observed this increase in the dorsal horn of the spinal cord in the 56th day. It was observed an increase in immunoexpression of ATF3 in DRG and spinal cord of dorsal horn in all treated groups in the 28th and 56th days. iNOS immunofluorescence showed no significant difference between groups in the DRG nor spinal cord, already in the 28th day, there was an increase in immunoexpression of iNOS in GRD. Thus, the results showed that the oxalate may be partially involved in PSN induced OXL.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Oxaliplatina (OXL) à um agente platÃnico de 3 geraÃÃo com potente atividade citotÃxica em diversos cÃnceres. Tem como toxicidade limitante uma neuropatia sensitiva perifÃrica (NSP) de inÃcio agudo, tornando-se crÃnica com doses cumulativas. Amifostina (AMF) à um agente antioxidante de largo espectro, que vem sendo atualmente estudado na citoproteÃÃo dos efeitos adversos da radioterapia e quimioterapia do cÃncer. Esta pesquisa objetivou avaliar o efeito da AMF sobre a hiperalgesia mecÃnica plantar e alodinia tÃrmica, assim como sobre as alteraÃÃes histopatolÃgicas e imunoexpressÃo de marcadores, tais como a proteÃna c-Fos, caspase 3, IL-1, nitrotirosina, NOSi, NOSn e NMDA, observadas na NSP experimental induzida por OXL. O estudo foi aprovado pelo Comità de Ãtica em Pesquisa Animal da Universidade Federal do CearÃ, com o protocolo 27/08. Camundongos Swiss machos (25-35g) foram tratados com OXL (1mg/kg, i.v.) e prÃ-tratados com AMF (1, 5, 25, 50 ou 100mg/kg, s.c.) por 4,5 semanas, paralelamente aos testes nociceptivos. A alodÃnia tÃrmica foi avaliada pelo teste de imersÃo da cauda em Ãgua fria (10ÂC) e a hiperalgesia mecÃnica plantar pelo teste do Von Frey EletrÃnico. Foi realizada a anÃlise histopatolÃgica e imunohistoquÃmica de amostras obtidas do corno dorsal da medula espinhal lombar dos animais em 24h, 7, 14, 21 e 28 dias. Demonstrou-se que a OXL diminuiu significativamente o limiar nociceptivo mecÃnico e tÃrmico, a partir do 21 dia (p<0,001) e 14 dia (p<0,01), respectivamente, quando comparados ao grupo controle. O tratamento com AMF inibiu esses efeitos em todas as doses testadas (p<0,001), sendo a dose de 25mg/kg aquela com efeito mais significativo. No teste do Rota-Rod nÃo foi observada variaÃÃo significativa entre os grupos, indicando ausÃncia de comprometimento motor. Na anÃlise histopatolÃgica foram observados edema do tecido nervoso e atrofia dos neurÃnios nos animais tratados com OXL, o que nÃo ocorreu nos animais prÃ-tratados com AMF. Observou-se a imunoexpressÃo importante de c-Fos, caspase 3, NOSn, NOSi e nitrotirosina nos animais tratados apenas com OXL, e uma imunoexpressÃo reduzida do receptor NMDA, quando comparado com o grupo controle. AMF reduziu a expressÃo de c-Fos e de nitrotrosina, mas nÃo da caspase 3, NOSn e NOSi, e aumentou a expressÃo do receptor NMDA. NÃo houve imunoexpressÃo de IL-1 nos grupos testados. Embora preliminares, os dados sugerem que a AMF promoveu uma importante proteÃÃo nas alteraÃÃes sensitivas da NSP induzida por OXL, desde que inibiu a hiperalgesia e a alodinia, alÃm da imunoexpressÃo de c-Fos. Adicionalmente AMF promoveu importante aÃÃo protetora nas lesÃes teciduais, sendo capaz de exercer aÃÃo antioxidante e antiapoptÃtica, atravÃs da inibiÃÃo da expressÃo de nitrotirosina e do aumento da expressÃo do receptor NMDA, respectivamente. / Oxaliplatin (OXP) is a third-generation platinum agent with potent cytotoxic activity in several cancers. Its limiting toxicity is a sensory peripheral neuropathy (SPN) of acute onset, which becomes chronic after cumulative doses. Amifostine (AMF) is a broad spectrum antioxidant and is currently being studied as a cell-protecting agent against the adverse effects of radiotherapy and chemotherapy in cancer patients. This study was aimed to evaluate the effect of AMF on plantar mechanical hyperalgesia and thermal allodynia, as well as on histopathological alterations and immune expression of markers such as c-Fos protein, caspase 3, IL-1, nitrotyrosine, iNOS, nNOS and NMDA, observed in experimental OXL-induced SPN. The study was approved by the Ethics Committee on Animal Research, Federal University of CearÃ, through protocol 27/08. Male Swiss mice (25-35g) were treated with OXL (1 mg/kg, i.v.) and pre-treated with AMF (1, 5, 25, 50 or 100 mg/kg, s.c.) for 4,5 weeks, in addition to the performance of nociceptive tests. Thermal allodynia was evaluated by tail immersion in cold water (10ÂC), and plantar mechanical hyperalgesia by the Electronic Von Frey test. The histopathological and immunohistochemical analysis of samples taken from the dorsal horn of the lumbar spinal cord of the animals was performed in 24 hours, 7, 14, 21 and 28 days. OXP significantly decreased mechanic and thermal nociceptive threshold since 21th day (p<0,001) and 14th day (p<0,01), respectively, when compared to control group. AMF treatment inhibited these effects in all doses tested (p<0,001), and the dose of 25mg/kg had the most significant effect. Locomotor impairment was not evidenced through Rota-Rod test. Furthermore, we observed edema and neurons atrophy in dorsal horn of OXP group, not showed in AMF group. OXP group had overexpression of c-Fos, caspase 3, nNOS, iNOS, and nitrotyrosine, but a reduced NMDA receptor expression when compared to control group. AMF group had hypoexpression of c-Fos and nitrotyrosine and increased NMDA receptor expression, but not altered caspase 3, nNOS and iNOS expression. There was no immunoexpression of IL-1 in the tested groups. Although preliminary, the data suggest that AMF promoted an important protection in OXL-induced SPN sensory changes, since it inhibited the hyperalgesia and allodynia, as well as the immunoexpression of c-Fos. Additionally AMF promoted significant protective action on tissue lesions, being able to exert antioxidant and antiapoptotic action by inhibiting the expression of nitrotyrosine and increasing expression of NMDA receptors, respectively.

A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of MSc (Med) Johannesburg, 2011 / Peripheral sensory neuropathy is a common neurological complication of antiretroviral therapy, typically occurring within 6-months of starting Highly Active Antiretroviral Therapy (HAART) which includes stavudine. Therefore, the primary aim of the study was to determine the 6-month incidence of ATN in patients free of neuropathy and beginning stavudine-based HAART for the first time. Also, we examined whether initiating stavudine-based HAART altered the symptoms of patients who had a pre-existing, virus-mediated distal symmetrical polyneuropathy (HIV-DSP). Seventy-five HIV-positive patients were screened for neuropathy, at the Chris-Hani Baragwanath Hospital, using the AIDS Clinical Trials Group neuropathy screening tool. The bilateral presence of atleast one sign (decreased vibration sense in the great toe or absent ankle reflex) and one symptom (pain, paraesthesia or numbness) in the feet was indicative of neuropathy. On recruitment, 52 patients presented without neuropathy and 13 patients presented with HIV-DSP. After 3- months of follow-up (n=46), 23% (10/46) of patients had developed peripheral neuropathy, and by 6-months (n=44), 41% (18/44) of patients had developed neuropathy. Greater disease severity was the only risk factor significantly associated with the development of neuropathy. Eleven (61%) of the 18 patients that developed neuropathy, developed painful symptomatic neuropathy, and only 6 (55%) of these patients were receiving treatment for symptom relief. In patients with HIV-DSP, numbness was the most common symptom reported at baseline and was the only symptom to reduce in frequency across the 6-months. In conclusion, we found that the development of neuropathy is common in the first 6-months of patients initiating stavudine-based HAART.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

HIV-associated peripheral neuropathy (PN), and related functional limitations that affect the quality of life (QoL), may now be one of the most formidable challenges in the health care of people living with HIV (PLHIV). The most common PN is distal sensory polyneuropathy (DSP). It is likely that there is a high prevalence of PN among PLHIV in Rwanda. The available data on the prevalence of PN are poor and there are none on how PN is associated with functional abilities and the QoL of PLHIV, which can guide management. In addition, current management of PN is mostly related to symptomatic management and is mainly pharmacological which may not rehabilitate the neuromuscular function that has been affected by PN. This thesis planned to re-validate and adapt the lower extremity functional scale (LEFS) and the brief peripheral neuropathy screen (BPNS), establish the prevalence of PN, and determine the effects of physiotherapeutic exercises on PN, lower extremity functional limitations and QoL, among Rwandan PLHIV receiving antiretroviral therapy (ART). Methods Study 1 translated LEFS from English to Kinyarwanda, modified it accordingly, and tested its reliability among 50 adult PLHIV on ART. The study also piloted

Introdução: A Neuropatia auditiva/Dessincronia auditiva (NA) é um transtorno que foi identificado há apenas 20 anos, os pacientes que possuíam este transtorno eram diagnosticados como deficientes auditivos como conseqüência da falha no diagnóstico. Com o surgimento do registro das Emissões Otoacústicas e sua presença no repertório de testes de avaliação auditiva, foi possível ao clínico fazer o diagnóstico de NA. Assim sendo, é possível que alguns indivíduos que foram diagnosticados como portadores de uma perda auditiva neurossensorial, tivessem, na verdade, NA. Objetivos: O objetivo deste estudo foi caracterizar o tipo e grau da deficiência auditiva em uma população de deficientes auditivos da cidade de São Paulo; verificar a época da suspeita pelos pais da deficiência auditiva bem como do diagnóstico audiológico nestes indivíduos; identificar os participantes cujas avaliações comportamentais são incompatíveis com as avaliações eletrofisiológicas, visando identificar casos de Neuropatia Auditiva e realizar estudo qualitativo de casos dos participantes com incompatibilidade de respostas nas avaliações comportamentais e eletrofisiológicas. Método: Foram avaliados 89 deficientes auditivos de três escolas especiais da cidade de São Paulo e 11 do setor de Audiologia Educacional da Faculdade de Medicina da Universidade de São Paulo através de alguns testes audiológicos: imitanciometria, audiometria tonal limiar (ATL), emissões otoacústicas (EOA) e potencial evocado auditivo do tronco-encefálico (PEATE). Resultados: Dos 100 participantes deste estudo, 99% apresentaram uma deficiência auditiva do tipo neurossensorial e em 50% o grau predominante da deficiência auditiva foi profundo, um deles não conseguiu realizar a ATL. A média de idade da suspeita dos pais foi de 15,52 meses e o diagnóstico clínico foi de 25,07 meses, em todos os grupos a suspeita dos pais foi anterior ao diagnóstico. Apenas um participante apresentou avaliações comportamentais incompatíveis com as eletrofisiólogicas, todavia, no decorrer da pesquisa o quadro foi modificado, sendo que a flutuação da audição foi o fator mais marcante observado. Conclusões: Os resultados sugerem que a NA é um transtorno raro mesmo na população dos deficientes auditivos e alertam para a necessidade de acompanhar longitudinalmente os casos de suspeita do transtorno / Introduction: Auditory Neuropathy/Auditory Dys-synchrony (AN) is a disorder identified only 20 years ago. Due to diagnosis failure, patients with this disorder were diagnosed as hearing impaired. AN diagnosis was made possible upon the appearance of OAE\'s recordings and its presence in hearing evaluation battery. Therefore, it is possible that some individuals who have been diagnosed as suffering from sensorioneural hearing loss had indeed AN. Purpose: The purpose of this study was to characterize the type and degree of auditory impairment in a population of the hearing impaired in the city of São Paulo; to verify when parents had the suspicious of the hearing impairment and when was the audiological diagnosis done in these individuals; to identify the subjects whose behavioral evaluations are not compatible with the electrophysiological evaluations in order to identify Auditory Neuropathy events and carry out a qualitative study of the cases of subjects with incompatibility of responses in the behavioral and electrophysiological evaluations. Method: 89 hearing impaired individuals from three school for the deaf in the city of São Paulo, and 11 from the Educational Audiology Division of the Medicine School of the University of São Paulo were evaluated in some audiological tests: imitanciometry, audiometer evaluation (AE), otoacoustic emissions (OAE) and Auditory Brainstem Response (ABR). Results: Out of the 100 subjects in this study, 99% presented a sensorioneural hearing loss, and in 50% the predominant degree of auditory loss was profound, one of the subjects was not able to perform AE. The average age of parents suspicion was 15.52 months and the clinical diagnosis was 25.07 months, in all the groups the parents suspicion was prior to the formal diagnosis. Only one subject presented behavioral evaluations incompatible with the electrophysiological, however, in the course of the research the chart was changed, whereas the hearing fluctuation was the most remarkable factor observed. Conclusions: The results suggest that AN is a rare disorder even in the hearing impaired community and alert the need of long term follow up in the cases of suspected disorder

nÃo hà / IntroduÃÃo: A neurotoxicidade cumulativa à uma toxicidade que pode advir da terapia à base de oxaliplatina (OXL), que à a 3 geraÃÃo de agentes platinos com amplo espectro de atividade antitumoral, incluindo cÃncer colorretal, ovariano e pulmonar. A neurotoxicidade associada à OXL gera uma toxicidade dose-limitante, crÃnica, a neuropatia sensitiva perifÃrica (NSP). Objetivo: Investigar o envolvimento da endotelina-1, de receptores TRPV1 e NMDA e da substÃncia P envolvidos na patogÃnese da neuropatia sensitiva perifÃrica induzida pelo agente antineoplÃsico oxaliplatina. Materiais e mÃtodos: O estudo foi aprovado pelo Comità de Ãtica em Pesquisa Animal da UFC (protocolo n 75/12). Camundongos Swiss machos (20g) foram prÃ-tratados com antagonistas de receptores de endotelina-1 (Bosentana 100mg/kg, VO; BQ-123 e BQ-788 30Âl, intraplantar) e antagonistas do receptor TRPV1 (capsazepina, 5mg/kg, IP), antagonista do receptor NK-1 da Substancia P (apreptanto, 1mg/kg, IP) e antagonista de receptores NMDA (MK-801, 0,5mg/kg, IP) 30 minutos antes da administraÃÃo de OXL (1mg/kg, IV) por 4 semanas e meia. Paralelamente foram realizados testes nociceptivos para avaliar o desenvolvimento da neuropatia sensitiva perifÃrica. A hipernocicepÃÃo foi avaliada pelo teste de imersÃo da cauda (TIC) em Ãgua fria (10ÂC) ou aquecida (43ÂC) e pelo teste Von Frey (HPM). Em seguida, foi realizado imunofluorescÃncia do segmento medular e gÃnglio da raiz dorsal e RT-PCR. Resultados: Como resultados observou-se que com o prÃ-tratamento ao uso de OXL que houve atenuaÃÃo da hiperalgesia da NSP induzida por OXL. Ao realizar a administraÃÃo de antagonistas seletivos de endotelina-1 intraplantar na pata direita observou-se reduÃÃo significativa na hiperalgesia na pata direita (tratada) em comparaÃÃo à pata esquerda (controle). Ao analisar a expressÃo gÃnica para cFos, NK-1 e o receptor de endotelina B, observou-se que houve reduÃÃo significativa da expressÃo dos marcadores no grupo prÃ-tratado com Bosentana ao comparar com o grupo OXL, que demonstrou a expressÃo aumentada para esses marcadores. ConclusÃo: Conclui-se no presente estudo que hà evidÃncias do papel da endotelina-1, de receptores (TRPV1 e NMDA) e da substÃncia P na patogÃnese da NSP induzida pelo agente antineoplÃsico OXL. / Introduction: The cumulative neurotoxicity is a toxicity that can result from oxaliplatin-based therapy (OXL), which is the 3rd generation platinum agent with broad spectrum of antitumor activity, including colorectal, ovarian and lung cancer. Neurotoxicity associated with OXL generates a dose-limiting toxicity, chronic, peripheral sensory neuropathy (NSP). Objective: To investigate the involvement of endothelin-1, TRPV1 receptors and NMDA and substance P involved in the pathogenesis of peripheral sensory neuropathy induced by oxaliplatin antineoplastic agent. Methods: Male Swiss mice (20g) were pre-treated with antagonists of endothelin-1 receptors (Bosentan 100mg / kg orally; BQ-123 and BQ-788 30&#956;l, intraplantar) and TRPV1 receptor antagonists (capsazepine, 5mg / kg , IP), antagonist of NK-1 receptor for substance P (apreptanto, 1 mg / kg, IP), and a NMDA receptor antagonist (MK-801, 0.5mg / kg, IP) 30 minutes before administration of OXL (1mg / kg, IV) for 4.5 weeks. Parallel nociceptive tests performed to assess the development of peripheral sensory neuropathy. The hyperalgesia assessed by the tail immersion test (ICT) in cold water (10 C) or warm (43 C) and test Von Frey (HPM). Then it was performed spinal segment, and the dorsal root ganglion immunofluorescence and RT-PCR the Ethics Committee approved the study for Animal Research UFC (Protocol 75/12). Results: The results observed when using the antagonists, as a pretreatment to the use of OXL there was attenuation of the induced hyperalgesia (NSP) OXL. Upon administration of selective antagonists of endothelin in the right paw was significant reduction in paw hyperalgesia in the right (treated) compared to the left paw (control). By analyzing the gene expression of cFos, NK-1 and endothelin B receptor, it was observed that there was significant reduction of expression of the markers in pre-treated bosentan group versus OXL group that showed increased expression for these markers. Conclusion: It was concluded in this study that there is evidence of the role of endothelin-1 receptors (TRPV1 and NMDA) and substance SP in the pathogenesis of NSP induced antineoplastic agent OXL.

Introdução: A Neuropatia auditiva/Dessincronia auditiva (NA) é um transtorno que foi identificado há apenas 20 anos, os pacientes que possuíam este transtorno eram diagnosticados como deficientes auditivos como conseqüência da falha no diagnóstico. Com o surgimento do registro das Emissões Otoacústicas e sua presença no repertório de testes de avaliação auditiva, foi possível ao clínico fazer o diagnóstico de NA. Assim sendo, é possível que alguns indivíduos que foram diagnosticados como portadores de uma perda auditiva neurossensorial, tivessem, na verdade, NA. Objetivos: O objetivo deste estudo foi caracterizar o tipo e grau da deficiência auditiva em uma população de deficientes auditivos da cidade de São Paulo; verificar a época da suspeita pelos pais da deficiência auditiva bem como do diagnóstico audiológico nestes indivíduos; identificar os participantes cujas avaliações comportamentais são incompatíveis com as avaliações eletrofisiológicas, visando identificar casos de Neuropatia Auditiva e realizar estudo qualitativo de casos dos participantes com incompatibilidade de respostas nas avaliações comportamentais e eletrofisiológicas. Método: Foram avaliados 89 deficientes auditivos de três escolas especiais da cidade de São Paulo e 11 do setor de Audiologia Educacional da Faculdade de Medicina da Universidade de São Paulo através de alguns testes audiológicos: imitanciometria, audiometria tonal limiar (ATL), emissões otoacústicas (EOA) e potencial evocado auditivo do tronco-encefálico (PEATE). Resultados: Dos 100 participantes deste estudo, 99% apresentaram uma deficiência auditiva do tipo neurossensorial e em 50% o grau predominante da deficiência auditiva foi profundo, um deles não conseguiu realizar a ATL. A média de idade da suspeita dos pais foi de 15,52 meses e o diagnóstico clínico foi de 25,07 meses, em todos os grupos a suspeita dos pais foi anterior ao diagnóstico. Apenas um participante apresentou avaliações comportamentais incompatíveis com as eletrofisiólogicas, todavia, no decorrer da pesquisa o quadro foi modificado, sendo que a flutuação da audição foi o fator mais marcante observado. Conclusões: Os resultados sugerem que a NA é um transtorno raro mesmo na população dos deficientes auditivos e alertam para a necessidade de acompanhar longitudinalmente os casos de suspeita do transtorno / Introduction: Auditory Neuropathy/Auditory Dys-synchrony (AN) is a disorder identified only 20 years ago. Due to diagnosis failure, patients with this disorder were diagnosed as hearing impaired. AN diagnosis was made possible upon the appearance of OAE\'s recordings and its presence in hearing evaluation battery. Therefore, it is possible that some individuals who have been diagnosed as suffering from sensorioneural hearing loss had indeed AN. Purpose: The purpose of this study was to characterize the type and degree of auditory impairment in a population of the hearing impaired in the city of São Paulo; to verify when parents had the suspicious of the hearing impairment and when was the audiological diagnosis done in these individuals; to identify the subjects whose behavioral evaluations are not compatible with the electrophysiological evaluations in order to identify Auditory Neuropathy events and carry out a qualitative study of the cases of subjects with incompatibility of responses in the behavioral and electrophysiological evaluations. Method: 89 hearing impaired individuals from three school for the deaf in the city of São Paulo, and 11 from the Educational Audiology Division of the Medicine School of the University of São Paulo were evaluated in some audiological tests: imitanciometry, audiometer evaluation (AE), otoacoustic emissions (OAE) and Auditory Brainstem Response (ABR). Results: Out of the 100 subjects in this study, 99% presented a sensorioneural hearing loss, and in 50% the predominant degree of auditory loss was profound, one of the subjects was not able to perform AE. The average age of parents suspicion was 15.52 months and the clinical diagnosis was 25.07 months, in all the groups the parents suspicion was prior to the formal diagnosis. Only one subject presented behavioral evaluations incompatible with the electrophysiological, however, in the course of the research the chart was changed, whereas the hearing fluctuation was the most remarkable factor observed. Conclusions: The results suggest that AN is a rare disorder even in the hearing impaired community and alert the need of long term follow up in the cases of suspected disorder

Vinte e seis pacientes com paralisia facial unilateral de longa duração foram submetidos à reanimação facial em único estágio com transplante do músculo grácil inervado pelo ramo massetérico do nervo trigêmeo. Foram divididos em 2 grupos não-randomizados de acordo com a técnica de fixação: Grupo I (19 pacientes), fixação do músculo com uso do tendão palmar longo inserido no músculo orbicular nos lábios superior e inferior do lado não paralisado (além da linha média); Grupo II (7 pacientes), fixação do retalho apenas com pontos separados no músculo orbicular dos lábios superior e inferior no lado paralisado. A avaliação qualitativa demonstrou melhores resultados no Grupo I (94,1% vs 66,6%). Na comparação do posicionamento do arco de cúpido em repouso, no pré e pós-operatório, observamos melhora estatisticamente significante (p<0,05) em ambos os grupos. Durante o sorriso, entretanto, houve melhora significativamente maior na centralização do arco de cúpido nos pacientes submetidos à fixação com tendão palmar longo (Grupo I) / Twenty-six patients with unilateral long-stading facial palsy underwent 1-stage reanimation with free gracilis muscle transplant innervated by the masseteric branch of the trigeminal nerve. They were divided into 2 nonrandomized groups according to insertion technique: group I (19 patients), palmaris longus tendon graft placed between the gracilis free flap and the orbicularis oris of the upper and lower lip on the nonparalyzed side; group II (7 patients), interrupted suture between the free flap and the orbicularis oris of the upper and lower lip on the paralyzed side. Qualitative evaluation of the smile demonstrated better results in patients from group I (94,1% vs 66,6%). Comparing the position of the Cupid`s bow at rest, pre- and postoperatively in each patient, we observed significant improvement of facial symmetry in both groups. During smile, however, there was significantly higher rate of centralization of the Cupid`s bow in patients submitted to reanimation with the use of the palmaris longus tendon (group I)