A infusão intratecal de fármacos analgésicos é método considerado útil no tratamento da dor decorrente do câncer. Entretanto, estudos sobre eficácia no tratamento prolongado da dor crônica não decorrente de câncer são escassos. Este trabalho objetivou analisar prospectivamente o resultado do tratamento de 80 doentes com dor crônica não decorrente de câncer com infusão intratecal de morfina. Os resultados foram avaliados quanto à intensidade, características e etiologias da dor, qualidade de vida e complicações dos procedimentos; 42 doentes eram do sexo masculino, a média das idades foi de 48,4 anos e a duração média da condição álgica foi de 53 meses. A dor decorreu de mielopatia em 26,3% dos doentes, de síndrome dolorosa miofascial em 6,3%, de síndrome dolorosa pós-laminectomia em 23,8%, de síndrome complexa de dor regional em 8,8%, de síndrome fibromiálgica em 13,8% e de neuralgia pós herpética em 5,0%. Apresentavam dor neuropática 49 (61,2%), nociceptiva 19 (23,8%) e mista 12 (15%) pacientes. Foram implantadas 62 bombas de acionamento digital para infusão em bolo e 18 bombas de infusão contínua (gás) ou programável. As médias das intensidades da dor reduziram-se de 9,5 para 4,6 segundo a escala visual analógica (EVA) ao final do acompanhamento que variou de 18 a 98 meses (média = 46,7 meses); houve melhora significativa da dor nos doentes com dor neuropática (p < 0,001), nociceptiva (p < 0,001) ou mista (p = 0,005). Apesar da melhora da qualidade de vida de acordo com SF-36 (30,8 para 49,6) e nas dimensões do Questionário \"Treatment of Pain Survey\" (TOPS), não houve alteração na capacidade objetiva para o trabalho. Não houve diferença significativa entre infusão contínua e em bolo quanto à melhora da dor (p = 0,597). O consumo de morfina estabilizou-se após o sexto mês de tratamento na maioria dos casos. Não houve diferença significativa quanto à melhora em relação à localização da extremidade do cateter subaracnóideo (p = 0,227). Ocorreu agravamento da dor de 4,9 para 8,9 (p < 0,001) durante o período de uso de medicação placebo. Alguns efeitos adversos ocorreram inicialmente e geralmente foram toleráveis. Conclui-se que a infusão intratecal de opióides é método adequado e seguro para o tratamento da dor crônica rebelde não decorrente do câncer. / Implantable pumps for intrathecal delivery of opiates are efficient for treatment of cancer pain. However, studies of nonmalignant pain with long term follow-up are few. The present study use prospective analysis of the result of the long term treatment of 80 patients presenting nonmalignant pain with intrathecal infusion of morphine. The nature and etiology of the pain, quantitative and qualitative expressions of pain and the quality of the life before and at the end of the treatment and complications of procedures were evaluated; were male 42 (52%) patients, the average of the ages was 48.4 years and the mean duration of previous pain, 53 months. Pain was due to mielopathy in 26.3% of the cases, myofascial pain syndrome in 6.3%, failed back pain in 23.8%, complex regional pain syndrome in 8.8%, fibromyalgia in 13.8% and post-herpetic neuralgia in 5.0%. Presented as neuropathic pain 49 (61.2%) patients, as nociceptive pain 19 (23.8%) patients and as mixed pain 12 (15%) patients. In 62 patients pumps for self-administration bolus of morphine was implanted and in 18 constant-flow(gas) or programable pumps. The mean intensity of pain according the visual analogical scale (VAS) reduced from 9.5 to 4.6 at the end of 46.7 months (18 to 98 months) mean follow-up; there was significant improvement of the results in neuropathic(p < 0.001), nociceptive(p < 0.001) and mixed pain(p = 0.005). There was improvement of the quality of life measured by SF-36(30.8 to 49.6) and in all dimensions of the Questionnaire \"Treatment of Pain Survey\" (TOPS), except in working capacity. There was no significant difference of the results for patients treated with bolus or constant flow pumps (p = 0.597). The daily dose of morphine became constant after six month of treatment in the majority of the cases. The position of the tip of the cateter did not influenced improvement in pain intensity (p = 0.277). Patients treated with placebo had increasing of pain intensity from 4.9 to 8.9 according the VAS (p < 0,001). Side effects were more frequent at the beginning of the treatment and few were intolerable. Concluded that intrathecal infusion of morphine is a suitable and safe method for treatment of chronic nonmalignant pain.

In Europe, Lyme disease is caused by the species Borrelia (B.) burgdorferi sensu stricto, B. garinii and B. afzelii. The disease is the most common vector-borne infection in Europe and the United States, and the resulting manifestation can involve the skin, nervous system, heart and joints. The symptoms that arise are associated with the Borrelia species causing the infection. The species most associated with neuroborreliosis is B. garinii whilst B. burgdorferi sensu stricto is associated with arthritis and B. afzelii is associated with dermatological symptoms. Lyme disease normally has three phases in untreated patients. The first phase is characterised by erythema migrans, a reddening of the skin around the area of the tick bite. If the disease develops to the second phase the patient will suffer from neuroborreliosis which is characterised by neurological symptoms such as headache and peripheral facial paralysis. Cerebrospinal fluid (CSF) analysis is used to diagnose neuroborreliosis. The diagnosis is complicated by variations between the different Borrelia species and that many healthy individuals have antibodies directed against Borrelia. Antibodies in CSF can be found in different diseases. The antibodies can be produced in the central nervous system or come across the blood-brain barrier and thus derive originally from the blood. By measuring the concentration of total albumin in serum and in CSF it can be determined if the antibodies present in the CSF have been produced in the central nervous system or if they originate from the blood. The typical manifestation in the last phase of Lyme disease is severe arthritis. The aim of this examination project was to compare two ELISAs for detection of antibodies directed to Borrelia. Indirect ELISAs from DAKO and Euroimmun were compared for the diagnosis of neuroborreliosis in 100 individuals. Borrelia specific antibodies of class IgM or IgG were found in 16 of 100 patients by DAKO’s ELISA and in 20 of the same 100 patients by Euroimmun’s ELISA. The reason that Euroimmun’s method detected more cases of neuroborreliosis is probably that this method detects antibodies directed to all three pathological species of Borrelia while DAKO’s method only detects antibodies directed to B. burgdorferi. In conclusion, this study indicates that Euroimmun’s method to detect antibodies of class IgM and IgG directed to Borrelia is superior to DAKO’s method. The obtained results were confirmed by Western blot analysis which gave results in accordance with those of Euroimmun’s ELISA.

The pharmacologic treatment of painful neuropathy continues to pose problems and challenges in clinical practice. This is largely due to a limited understanding of the underlying etiologies of such neuropathic pain and insufficient knowledge of the optimal effective doses that would cause only minimal systemic side effects. The use of molecular methods, such as gene deletion from knockout mice and the development of cellular mini-pumps for the delivery of biologic antinociceptive molecules have led to a better understanding of the underlying mechanisms involved in the induction of intractable neuropathic pain. It is now known that the initiation of an excitatory cascade after injury or disease leads to the induction of various second messenger systems, and the loss or down-regulation of the endogenous inhibitory spinal system and central sensitization, both of which cause such pain. Currently, there are novel approaches that use genetic therapy in the management of neuropathic pain. Two such approaches which have been determined to be safe are proposed to be investigated in this study using animal models of pain. The first approach involves cell-mediated delivery of antinociceptive molecules to the cerebrospinal fluid using cultivated spinal progenitor cells transplanted into the subarachnoid space. Chronic constriction injury (CCI) of the sciatic nerve was used to induce chronic neuropathic pain in the hind paw of rats. 1x106 spinal progenitor cells (SPCs) were implanted intrathecally on the third day after the CCI surgery. The behavioral response to thermal hyperalgesia was observed and recorded during the 14 days post surgery. Various techniques were utilized to trace the progenitor cells, confirm the differentiation, and identify the neurotransmitters involved. Glutamic acid decarboxylase (GAD) immunoreactivity was revealed for 65% of the cultivated SPCs in our study. We also determined that transplanted cells could survive more than four weeks post intrathecal implantation. Significant reductions were demonstrated for responses to thermal stimuli for the CCI rats that had received intrathecal SPC transplantation. A novel intrathecal delivery with SPCs reduced CCI-induced neuropathic pain. The second approach involves the use of a newly developed intrathecal electroporation probe in the delivery of antinociceptive peptides to reduce expression of endogenous nociceptive molecules in the spinal cord. To investigate the feasibility of delivering exogenous genes into spinal cord using direct in vivo electrotransfection, pE-GFP C1 vector was used to achieve the goal. Gene transfer to the spinal cord was accomplished via direct intrathecal injection of, followed by 5 electric pulses for 50 ms at 200 V delivered intrathecally. The spinal cords were retrieved and analyzed with fluorescence microscopy, reverse transcription polymerase chain reaction (RT-PCR), and western blotting. At day 1, 3 or 7 following electroporation a clear green fluorescence protein (GFP) expression in spinal cord tissue was detected. The most prominent transfection occurred in the meningeal cells and superficial layer of the spinal cord. Successful transfection was also confirmed with RT-PCR and western blotting. The expression of GFP protein was peaked between 3-7 days after electroporation and significantly decreased at 14 days. No behavioral or spinal neurodegenerative changes were detected at any time point. This study demonstrates that direct in vivo electrotransfection represents an effective and simple method for spinal gene delivery. Furthermore, the optimal pulse characteristics (voltage, pulse duration, number of shocks) were investigated for in vivo electroporation for gene transfer into the spinal cord. The expression of pre-opiomelanocortin (POMC) gene from electroporated plasmid DNA was then evaluated in this study using RT-PCR and western blot. We conclude that the optimal conditions for electroporation are a pulse voltage of 200 V, 75-ms duration, 925-ms interval, for five iterations. Also, electroporation treatment for neuropathic pain was attempted for CCI rats using plasmid DNA that expresses the POMC gene. Intrathecal administrations of the POMC plasmid elevated spinal beta-endorphin levels, as manifested in significantly elevated pain threshold for the CCI limbs. We also tested whether intrathecal electric stimulation would reduce the tolerance of chronic morphine usage and the severity of precipitated morphine withdrawal symptoms. Rats received intrathecal electrode catheter implantation and a continuous intrathecal infusion of morphine (2 nmol/hr) or saline for seven days. Intrathecal electric stimulations (0, 20V, 200V) were performed once daily during the same period. Daily tail flick and intrathecal morphine challenge tests were performed to assess the effect of intrathecal electric stimulation on antinociception and tolerance of morphine. Naloxone withdrawal (2mg/kg) was performed to assess morphine dependence, and changes in spinal neurotransmitters were monitored by microdialysis. The antinoceptive effect of intrathecal morphine was increased by 200V electric stimulation. The magnitude of tolerance was decreased in the rats receiving 2 nmol/hr infusion with daily intrathecal electric stimulation. The severity of naloxone-induced withdrawal symptom was lower in the rats receiving 200V stimulation. Intrathecal stimulation thus enhances analgesia and attenuates naloxone-induced withdrawal symptoms in rats receiving chronic intrathecal morphine infusion. Increases in spinal glycine release may be the underlying mechanisms. The promise is that, both approaches attenuate or reverse persistent nociceptive states; they could be exploited for use in the development of gene therapy for the management of pain.

Introdução e Objetivos: O sistema nervoso central (SNC) é o um sítio freqüente de recaída na criança com leucemia linfocítica aguda (LLA). Existe evidência de que a punção lombar traumática (PLT) pode representar um risco adicional de recaída no SNC quando ocorre inoculação de blastos no liqüido céfalorraquidiano (LCR). Este estudo tem por objetivo determinar se a ocorrência da PLT ao diagnóstico afeta o prognóstico de pacientes com essa patologia. Material e Métodos: Setenta e sete pacientes com diagnóstico de LLA, tratados entre 1992 a 2002, foram incluídos na análise. Quimioterapia intratecal (QIT) foi instilada imediatamente após a PL inicial (precoce), ou na segunda PL (tardia), realizada no período de 24 a 48 horas após a realização da PL inicial. Foi feita análise da influência da PLT e do momento (precoce x tardia) de administração da QIT em relação a recaída no SNC. Resultados: Entre os 19 pacientes que apresentaram PLT ao diagnóstico e receberam QIT tardia, seis tiveram recaída isolada no SNC e dois recaída combinada em SNC e medula óssea (MO). Entre os nove pacientes que tiveram PLT e receberam QIT precoce, somente um apresentou recaída combinada em SNC e MO (P=0,20); não houve, portanto, influência estatisticamente significativa da PLT na sobrevida livre de eventos (SLE) (55% para QIT precoce x 49% para QIT tardia) (P=0,37). Entretanto, em análise estratificada, de acordo com grupos de risco, observamos que para pacientes de baixo ou médio risco o OR foi de 0,8 quando recebiam QIT tardia (P=0,99) e 0,17 quando recebiam QIT precoce (P=0,47). Por outro lado, entre pacientes de alto risco o OR para recaída foi de 21,0 para aqueles que recebiam QIT tardia (P=0,09) e 1,5 para o grupo que recebia Q IT precoce (P=0,99). Conclusão: Os resultados do presente estudo são sugestivos de que a ocorrência da PLT tem uma influência adversa no prognóstico de pacientes com LLA de alto risco de recaída. Como estes resultados são decorrentes de um estudo retrospectivo, recomenda-se que sejam confirmados em estudos prospectivos randomizados. / Introduction and Objectives: The Central Nervous System (CNS) is a frequent site of relapse in childhood acute lymphoblastic leukemia (ALL). Traumatic lumbar puncture (TLP) is thought to increase the risk of relapse in the CNS. This study sought to determine if TLP at the time of diagnosis affected the outcome of patients. Matherial and Methods: Seventy-seven newly diagnosed patients treated from 1992 to 2002 were included in the analysis. Intrathecal therapy (IT) was instilled either immediately after the diagnostic LP (early) or at a second LP (delayed) 24 to 48 hours following the diagnostic LP procedure. The authors carried out an analysis of the influence of TLP and the timing (early versus late) of administration of IT therapy on CNS relapse. Results: Among the 19 patients who had a TLP at diagnosis and received late IT therapy, six had isolated CNS relapse and two had combined CNS and bone marrow (BM) relapse. Among the nine patients who had TLP and received early IT therapy, only one had a combined CNS and BM relapse (P=0.20); the influence of TLP was not statistically significant on the event-free survival (EFS) (55% for early IT versus 49% for delayed IT) ( P =0.37). However, when we carried out a stratified analysis according to risk categories we found that for low and standard risk patients the odds ratio (OR) for relapse was 0.8 for delayed IT therapy (P=0.99) and 0.17 for early IT (P=0.47). On the other hand, among high risk (HR) patients the OR for relapse was 21.0 for delayed IT therapy (P=0.09) and 1.5 for early IT (P=0.99). Conclusion: The occurrence of TLP impacts adversely on prognosis of HR ALL patients. As these results are based in a retrospective study with a low number of patients, the authors recommend future trials using prospective randomized studies to confirm these findings.

Introdução e Objetivos: O sistema nervoso central (SNC) é o um sítio freqüente de recaída na criança com leucemia linfocítica aguda (LLA). Existe evidência de que a punção lombar traumática (PLT) pode representar um risco adicional de recaída no SNC quando ocorre inoculação de blastos no liqüido céfalorraquidiano (LCR). Este estudo tem por objetivo determinar se a ocorrência da PLT ao diagnóstico afeta o prognóstico de pacientes com essa patologia. Material e Métodos: Setenta e sete pacientes com diagnóstico de LLA, tratados entre 1992 a 2002, foram incluídos na análise. Quimioterapia intratecal (QIT) foi instilada imediatamente após a PL inicial (precoce), ou na segunda PL (tardia), realizada no período de 24 a 48 horas após a realização da PL inicial. Foi feita análise da influência da PLT e do momento (precoce x tardia) de administração da QIT em relação a recaída no SNC. Resultados: Entre os 19 pacientes que apresentaram PLT ao diagnóstico e receberam QIT tardia, seis tiveram recaída isolada no SNC e dois recaída combinada em SNC e medula óssea (MO). Entre os nove pacientes que tiveram PLT e receberam QIT precoce, somente um apresentou recaída combinada em SNC e MO (P=0,20); não houve, portanto, influência estatisticamente significativa da PLT na sobrevida livre de eventos (SLE) (55% para QIT precoce x 49% para QIT tardia) (P=0,37). Entretanto, em análise estratificada, de acordo com grupos de risco, observamos que para pacientes de baixo ou médio risco o OR foi de 0,8 quando recebiam QIT tardia (P=0,99) e 0,17 quando recebiam QIT precoce (P=0,47). Por outro lado, entre pacientes de alto risco o OR para recaída foi de 21,0 para aqueles que recebiam QIT tardia (P=0,09) e 1,5 para o grupo que recebia Q IT precoce (P=0,99). Conclusão: Os resultados do presente estudo são sugestivos de que a ocorrência da PLT tem uma influência adversa no prognóstico de pacientes com LLA de alto risco de recaída. Como estes resultados são decorrentes de um estudo retrospectivo, recomenda-se que sejam confirmados em estudos prospectivos randomizados. / Introduction and Objectives: The Central Nervous System (CNS) is a frequent site of relapse in childhood acute lymphoblastic leukemia (ALL). Traumatic lumbar puncture (TLP) is thought to increase the risk of relapse in the CNS. This study sought to determine if TLP at the time of diagnosis affected the outcome of patients. Matherial and Methods: Seventy-seven newly diagnosed patients treated from 1992 to 2002 were included in the analysis. Intrathecal therapy (IT) was instilled either immediately after the diagnostic LP (early) or at a second LP (delayed) 24 to 48 hours following the diagnostic LP procedure. The authors carried out an analysis of the influence of TLP and the timing (early versus late) of administration of IT therapy on CNS relapse. Results: Among the 19 patients who had a TLP at diagnosis and received late IT therapy, six had isolated CNS relapse and two had combined CNS and bone marrow (BM) relapse. Among the nine patients who had TLP and received early IT therapy, only one had a combined CNS and BM relapse (P=0.20); the influence of TLP was not statistically significant on the event-free survival (EFS) (55% for early IT versus 49% for delayed IT) ( P =0.37). However, when we carried out a stratified analysis according to risk categories we found that for low and standard risk patients the odds ratio (OR) for relapse was 0.8 for delayed IT therapy (P=0.99) and 0.17 for early IT (P=0.47). On the other hand, among high risk (HR) patients the OR for relapse was 21.0 for delayed IT therapy (P=0.09) and 1.5 for early IT (P=0.99). Conclusion: The occurrence of TLP impacts adversely on prognosis of HR ALL patients. As these results are based in a retrospective study with a low number of patients, the authors recommend future trials using prospective randomized studies to confirm these findings.

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Agradecemos a compreensão. on 2018-04-19T13:02:09Z (GMT) / Submitted by DENISE MOROTO (de_moroto@hotmail.com) on 2018-04-19T14:03:21Z No. of bitstreams: 1 Tesev7.pdf: 10060555 bytes, checksum: bf4975d0b77a02d79ca9201cb11a74b8 (MD5) / Approved for entry into archive by Luciana Pizzani null (luciana@btu.unesp.br) on 2018-04-19T14:53:49Z (GMT) No. of bitstreams: 1 moroto_d_dr_bot.pdf: 10060555 bytes, checksum: bf4975d0b77a02d79ca9201cb11a74b8 (MD5) / Made available in DSpace on 2018-04-19T14:53:49Z (GMT). No. of bitstreams: 1 moroto_d_dr_bot.pdf: 10060555 bytes, checksum: bf4975d0b77a02d79ca9201cb11a74b8 (MD5) Previous issue date: 2018-02-21 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Introdução: Dor perioperatória desencadeia resposta neuroendócrina ao estresse, responsável por efeitos adversos em vários órgãos e sistemas. Estratégias foram desenvolvidas para controle da dor e dessa resposta ao trauma, como a injeção de dexametasona, glicocorticoide de alta potência, no espaço peridural e subaracnoideo. Embora a injeção de corticosteroides no neuroeixo seja realizada com aparentes benefícios em seres humanos no contexto da dor aguda e crônica, a eficácia e segurança desse procedimento continuam discutíveis e alvo de controvérsia na literatura. O objetivo deste estudo foi avaliar os efeitos histológicos que a dexametasona administrada no espaço subaracnoideo determina sobre o tecido nervoso da medula espinal e das meninges dos coelhos. Método: Após aprovação pela Comissão de Ética no Uso de Animais, 28 coelhos adultos jovens foram randomizados em dois grupos (G) experimentais com 14 animais cada: G1 recebeu solução salina a 0,9% pela via subaracnoidea e G2, dexametasona na dose de 0,37 mg.kg-1. Os animais foram mantidos em cativeiro por 21 dias, durante os quais se avaliou motricidade e sensibilidade dolorosa. Depois desse período, sob anestesia venosa, foram submetidos a sacrifício para retirada da porção lombar e sacral da medula espinal e das meninges para avaliação histológica pelo método de Hematoxilina-eosina (HE) e de marcação imuno-histoquímica para Proteína Glial Fibrilar Ácida (GFAP). Resultados: Todos os animais permaneceram sem alterações clínicas durante o período de cativeiro. Nenhum animal do G1 apresentou alterações histológicas à microscopia óptica. No G2, 13 animais exibiram infiltrado inflamatório linfoplasmocitário perivascular nos vasos das meninges, com ou sem acometimento também das meninges e do parênquima nervoso. Os animais do G2 também tiveram percentual de células marcadas pelo GFAP inferior aos do G1 (p<0,05). Conclusão: Neste modelo experimental em coelhos, a solução de dexametasona determinou alterações histológicas no tecido nervoso da medula espinal e, principalmente, nas meninges. / Background: Perioperative pain triggers neuroendocrine response to stress, responsible for adverse effects on various organs and systems. Strategies were developed to control pain and this response to trauma, such as the injection of dexamethasone, a high-potency glucocorticoid, into the epidural and subarachnoid space. Although corticosteroid spinal injection is performed with apparent benefits in humans in the context of acute and chronic pain, the efficacy and safety of this procedure remain controversial in the literature. The objective of this study was to evaluate the histological effects that dexamethasone administered into the subarachnoid space determines on the nervous tissue of the spinal cord and the meninges of rabbits. Methods: After approval by the animal research ethics committee, 28 young adult rabbits were randomized in two experimental groups (G) with 14 animals each: G1 received 0.9% saline solution into the intrathecal space and G2 received 0.37mg.kg-1 of dexamethasone by the same route. The animals were clinically evaluated for 21 days. After this period of observation, sacrifice was performed under intravenous anesthesia and then the lumbar and sacral portion of their spinal cords were removed for histological examination by Hematoxylin-eosin (HE) and Glial Fibrillary Acidic protein (GFAP) immunohistochemical staining. Results: All animals remained without clinical changes during the period of captivity. No histological changes were observed in G1 animals. In G2, 13 animals exhibited perivascular lymphoplasmocytic inflammatory infiltrate in the meninges vessels, with or without involvement of the meninges and the nervous parenchyma. G2 animals also showed lower percentage of GFAP stained cells than rabbits of G1 (p<0.05). Conclusion: In this experimental model, the dexamethasone solution determined histological changes in the nervous tissue of the spinal cord and, especially, the meninges of rabbits. / FAPESP: 2014/23740-2

Orientador: Eliana Marisa Ganem / Resumo: Introdução: Dor perioperatória desencadeia resposta neuroendócrina ao estresse, responsável por efeitos adversos em vários órgãos e sistemas. Estratégias foram desenvolvidas para controle da dor e dessa resposta ao trauma, como a injeção de dexametasona, glicocorticoide de alta potência, no espaço peridural e subaracnoideo. Embora a injeção de corticosteroides no neuroeixo seja realizada com aparentes benefícios em seres humanos no contexto da dor aguda e crônica, a eficácia e segurança desse procedimento continuam discutíveis e alvo de controvérsia na literatura. O objetivo deste estudo foi avaliar os efeitos histológicos que a dexametasona administrada no espaço subaracnoideo determina sobre o tecido nervoso da medula espinal e das meninges dos coelhos. Método: Após aprovação pela Comissão de Ética no Uso de Animais, 28 coelhos adultos jovens foram randomizados em dois grupos (G) experimentais com 14 animais cada: G1 recebeu solução salina a 0,9% pela via subaracnoidea e G2, dexametasona na dose de 0,37 mg.kg-1. Os animais foram mantidos em cativeiro por 21 dias, durante os quais se avaliou motricidade e sensibilidade dolorosa. Depois desse período, sob anestesia venosa, foram submetidos a sacrifício para retirada da porção lombar e sacral da medula espinal e das meninges para avaliação histológica pelo método de Hematoxilina-eosina (HE) e de marcação imuno-histoquímica para Proteína Glial Fibrilar Ácida (GFAP). Resultados: Todos os animais permaneceram sem alterações clíni... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: Perioperative pain triggers neuroendocrine response to stress, responsible for adverse effects on various organs and systems. Strategies were developed to control pain and this response to trauma, such as the injection of dexamethasone, a high-potency glucocorticoid, into the epidural and subarachnoid space. Although corticosteroid spinal injection is performed with apparent benefits in humans in the context of acute and chronic pain, the efficacy and safety of this procedure remain controversial in the literature. The objective of this study was to evaluate the histological effects that dexamethasone administered into the subarachnoid space determines on the nervous tissue of the spinal cord and the meninges of rabbits. Methods: After approval by the animal research ethics committee, 28 young adult rabbits were randomized in two experimental groups (G) with 14 animals each: G1 received 0.9% saline solution into the intrathecal space and G2 received 0.37mg.kg-1 of dexamethasone by the same route. The animals were clinically evaluated for 21 days. After this period of observation, sacrifice was performed under intravenous anesthesia and then the lumbar and sacral portion of their spinal cords were removed for histological examination by Hematoxylin-eosin (HE) and Glial Fibrillary Acidic protein (GFAP) immunohistochemical staining. Results: All animals remained without clinical changes during the period of captivity. No histological changes were observed in G1 anima... (Complete abstract click electronic access below) / Doutor

Introdução e Objetivos: O sistema nervoso central (SNC) é o um sítio freqüente de recaída na criança com leucemia linfocítica aguda (LLA). Existe evidência de que a punção lombar traumática (PLT) pode representar um risco adicional de recaída no SNC quando ocorre inoculação de blastos no liqüido céfalorraquidiano (LCR). Este estudo tem por objetivo determinar se a ocorrência da PLT ao diagnóstico afeta o prognóstico de pacientes com essa patologia. Material e Métodos: Setenta e sete pacientes com diagnóstico de LLA, tratados entre 1992 a 2002, foram incluídos na análise. Quimioterapia intratecal (QIT) foi instilada imediatamente após a PL inicial (precoce), ou na segunda PL (tardia), realizada no período de 24 a 48 horas após a realização da PL inicial. Foi feita análise da influência da PLT e do momento (precoce x tardia) de administração da QIT em relação a recaída no SNC. Resultados: Entre os 19 pacientes que apresentaram PLT ao diagnóstico e receberam QIT tardia, seis tiveram recaída isolada no SNC e dois recaída combinada em SNC e medula óssea (MO). Entre os nove pacientes que tiveram PLT e receberam QIT precoce, somente um apresentou recaída combinada em SNC e MO (P=0,20); não houve, portanto, influência estatisticamente significativa da PLT na sobrevida livre de eventos (SLE) (55% para QIT precoce x 49% para QIT tardia) (P=0,37). Entretanto, em análise estratificada, de acordo com grupos de risco, observamos que para pacientes de baixo ou médio risco o OR foi de 0,8 quando recebiam QIT tardia (P=0,99) e 0,17 quando recebiam QIT precoce (P=0,47). Por outro lado, entre pacientes de alto risco o OR para recaída foi de 21,0 para aqueles que recebiam QIT tardia (P=0,09) e 1,5 para o grupo que recebia Q IT precoce (P=0,99). Conclusão: Os resultados do presente estudo são sugestivos de que a ocorrência da PLT tem uma influência adversa no prognóstico de pacientes com LLA de alto risco de recaída. Como estes resultados são decorrentes de um estudo retrospectivo, recomenda-se que sejam confirmados em estudos prospectivos randomizados. / Introduction and Objectives: The Central Nervous System (CNS) is a frequent site of relapse in childhood acute lymphoblastic leukemia (ALL). Traumatic lumbar puncture (TLP) is thought to increase the risk of relapse in the CNS. This study sought to determine if TLP at the time of diagnosis affected the outcome of patients. Matherial and Methods: Seventy-seven newly diagnosed patients treated from 1992 to 2002 were included in the analysis. Intrathecal therapy (IT) was instilled either immediately after the diagnostic LP (early) or at a second LP (delayed) 24 to 48 hours following the diagnostic LP procedure. The authors carried out an analysis of the influence of TLP and the timing (early versus late) of administration of IT therapy on CNS relapse. Results: Among the 19 patients who had a TLP at diagnosis and received late IT therapy, six had isolated CNS relapse and two had combined CNS and bone marrow (BM) relapse. Among the nine patients who had TLP and received early IT therapy, only one had a combined CNS and BM relapse (P=0.20); the influence of TLP was not statistically significant on the event-free survival (EFS) (55% for early IT versus 49% for delayed IT) ( P =0.37). However, when we carried out a stratified analysis according to risk categories we found that for low and standard risk patients the odds ratio (OR) for relapse was 0.8 for delayed IT therapy (P=0.99) and 0.17 for early IT (P=0.47). On the other hand, among high risk (HR) patients the OR for relapse was 21.0 for delayed IT therapy (P=0.09) and 1.5 for early IT (P=0.99). Conclusion: The occurrence of TLP impacts adversely on prognosis of HR ALL patients. As these results are based in a retrospective study with a low number of patients, the authors recommend future trials using prospective randomized studies to confirm these findings.

A infusão intratecal de fármacos analgésicos é método considerado útil no tratamento da dor decorrente do câncer. Entretanto, estudos sobre eficácia no tratamento prolongado da dor crônica não decorrente de câncer são escassos. Este trabalho objetivou analisar prospectivamente o resultado do tratamento de 80 doentes com dor crônica não decorrente de câncer com infusão intratecal de morfina. Os resultados foram avaliados quanto à intensidade, características e etiologias da dor, qualidade de vida e complicações dos procedimentos; 42 doentes eram do sexo masculino, a média das idades foi de 48,4 anos e a duração média da condição álgica foi de 53 meses. A dor decorreu de mielopatia em 26,3% dos doentes, de síndrome dolorosa miofascial em 6,3%, de síndrome dolorosa pós-laminectomia em 23,8%, de síndrome complexa de dor regional em 8,8%, de síndrome fibromiálgica em 13,8% e de neuralgia pós herpética em 5,0%. Apresentavam dor neuropática 49 (61,2%), nociceptiva 19 (23,8%) e mista 12 (15%) pacientes. Foram implantadas 62 bombas de acionamento digital para infusão em bolo e 18 bombas de infusão contínua (gás) ou programável. As médias das intensidades da dor reduziram-se de 9,5 para 4,6 segundo a escala visual analógica (EVA) ao final do acompanhamento que variou de 18 a 98 meses (média = 46,7 meses); houve melhora significativa da dor nos doentes com dor neuropática (p < 0,001), nociceptiva (p < 0,001) ou mista (p = 0,005). Apesar da melhora da qualidade de vida de acordo com SF-36 (30,8 para 49,6) e nas dimensões do Questionário \"Treatment of Pain Survey\" (TOPS), não houve alteração na capacidade objetiva para o trabalho. Não houve diferença significativa entre infusão contínua e em bolo quanto à melhora da dor (p = 0,597). O consumo de morfina estabilizou-se após o sexto mês de tratamento na maioria dos casos. Não houve diferença significativa quanto à melhora em relação à localização da extremidade do cateter subaracnóideo (p = 0,227). Ocorreu agravamento da dor de 4,9 para 8,9 (p < 0,001) durante o período de uso de medicação placebo. Alguns efeitos adversos ocorreram inicialmente e geralmente foram toleráveis. Conclui-se que a infusão intratecal de opióides é método adequado e seguro para o tratamento da dor crônica rebelde não decorrente do câncer. / Implantable pumps for intrathecal delivery of opiates are efficient for treatment of cancer pain. However, studies of nonmalignant pain with long term follow-up are few. The present study use prospective analysis of the result of the long term treatment of 80 patients presenting nonmalignant pain with intrathecal infusion of morphine. The nature and etiology of the pain, quantitative and qualitative expressions of pain and the quality of the life before and at the end of the treatment and complications of procedures were evaluated; were male 42 (52%) patients, the average of the ages was 48.4 years and the mean duration of previous pain, 53 months. Pain was due to mielopathy in 26.3% of the cases, myofascial pain syndrome in 6.3%, failed back pain in 23.8%, complex regional pain syndrome in 8.8%, fibromyalgia in 13.8% and post-herpetic neuralgia in 5.0%. Presented as neuropathic pain 49 (61.2%) patients, as nociceptive pain 19 (23.8%) patients and as mixed pain 12 (15%) patients. In 62 patients pumps for self-administration bolus of morphine was implanted and in 18 constant-flow(gas) or programable pumps. The mean intensity of pain according the visual analogical scale (VAS) reduced from 9.5 to 4.6 at the end of 46.7 months (18 to 98 months) mean follow-up; there was significant improvement of the results in neuropathic(p < 0.001), nociceptive(p < 0.001) and mixed pain(p = 0.005). There was improvement of the quality of life measured by SF-36(30.8 to 49.6) and in all dimensions of the Questionnaire \"Treatment of Pain Survey\" (TOPS), except in working capacity. There was no significant difference of the results for patients treated with bolus or constant flow pumps (p = 0.597). The daily dose of morphine became constant after six month of treatment in the majority of the cases. The position of the tip of the cateter did not influenced improvement in pain intensity (p = 0.277). Patients treated with placebo had increasing of pain intensity from 4.9 to 8.9 according the VAS (p < 0,001). Side effects were more frequent at the beginning of the treatment and few were intolerable. Concluded that intrathecal infusion of morphine is a suitable and safe method for treatment of chronic nonmalignant pain.

Ultrasound-guided selective C5 nerve root blocks have been described in several case reports as a safe and effective means to anesthetize the distal clavicle while maintaining innervation of the upper extremity and preserving diaphragmatic function. In this study, cadavers were injected with 5 mL of 0.5% methylene blue dye under ultrasound guidance to investigate possible proximal and distal spread of injectate along the brachial plexus, if any. Following the injections, the specimens were dissected and examined to determine the distribution of dye and the structures affected. One injection revealed dye extended proximally into the epidural space, which penetrated the dura mater and was present on the spinal cord and brainstem. Dye was noted distally to the divisions in 3 injections. The anterior scalene muscle and phrenic nerve were stained in all 4 injections. It appears unlikely that local anesthetic spread is limited to the nerve root following an ultrasound-guided selective C5 nerve root injection. Under certain conditions, intrathecal spread also appears possible, which has major patient safety implications. Additional safety measures, such as injection pressure monitoring, should be incorporated into this block, or approaches that are more distal should be considered for the acute pain management of distal clavicle fractures.