Adaptação de longo prazo ao treinamento cíclico induzido eletricamente em indivíduos com severa lesão na medula espinhal

Indivíduos com lesão da medula espinhal (LME) mais freqüentemente adquirem essa condição na juventude e são relegados a uma vida de maior ou menor inatividade física. Em adição às implicações primárias da LME, indivíduos com LME severa são estigmatizados e relegados a uma condição de vida física inativa. É desconhecido se essas condições relatadas são potencialmente reversíveis e o objetivo do presente estudo foi, portanto, examinar os efeitos do exercício em indivíduos com LME. Então, 10 indivíduos (6 com tetraplegia e 4 com paraplegia; idade de 27 a 45 anos; tempo de lesão de 3 a 23 anos) foram treinados por 1 ano em cicloergometria com estimulação elétrica controlada por feedback. Eles treinaram 3 vezes por semana (média 2,3 vezes), 30 minutos em cada sessão. Os músculos glúteos, isquiotibiais e quadríceps foram estimulados por eletrodos colocados na superfície da pele sobre seus pontos motores. Durante o primeiro treino, uma variação substancial na performance foi observada entre os pacientes. A maioria dos indivíduos foi capaz de realizar o exercício por 30 minutos na primeira sessão, mas dois indivíduos foram capazes de realizar o exercício por apenas poucos minutos. Depois do treino de 1 ano, todos os indivíduos foram capazes de realizar 30 minutos contínuos de treino e o trabalho produzido teve aumento de 4 ± 1 (média de “erro-padrão” EP) para 17 ± 2 kJ por sessão de treino (P < 0,05). A taxa de captação máxima de O2 durante o exercício com estimulação elétrica aumentou de 1,20 ± 0,08 l/min, mensurada depois de poucas semanas de exercício, para 1,43 ± 0,09 l/min após 1 ano de treinamento (P < 0,05). Imagens de corte com ressonância magnética foram feitas na coxa para avaliar a massa muscular, que teve um aumento de 12% (média, P < 0,05) em 1 ano de treinamento. Em biópsias feitas antes do exercício, vários estados de atrofia foram observados nas fibras musculares dos indivíduos, um fenômeno que foi parcialmente normalizado em todos os pacientes depois do treinamento. É sabido que a distribuição do tipo de fibra no músculo esquelético é alterada para fibras do tipo II B (contração rápida, rapidamente fatigável, glicolíticas) dentro dos primeiros 2 anos após a lesão medular. Nessa avaliação, os músculos continham 63% de miosina de cadeia pesada (MHC) isoforme II B, 33% de MHC isoforme II A (contração rápida e resistentes à fadiga) e menos de 5% de MHC isoforme I (fibras de contração lenta) antes do treinamento. Uma transformação para obterem-se fibras com proteínas contráteis mais resistentes à fadiga foi encontrada após 1 ano de treinamento. A porcentagem de MHC isoforme II A aumentou para 61% do total de proteínas contráteis e houve uma diminuição de 32% nas fibras rapidamente fatigáveis do tipo MHC isoforme II, enquanto as MHC isoformes I somente compunham 7% da quantidade total de MHC. Essa alteração foi acompanhada de um aumento de 100% na atividade enzimática da citrato sintetase, como um indicador da capacidade oxidativa mitocondrial. Conclui-se que as alterações na performance, nesse exercício e nas características do músculo esquelético, associadas à inatividade que ocorre em indivíduos com LME, são reversíveis, mesmo até 20 anos após a lesão. Sucede que o treino com exercícios induzidos por estimulação elétrica dos músculos paralisados é uma efetiva ferramenta de reabilitação que deveria ser oferecida aos indivíduos com LME no futuro.Spinal cord injured (SCI) individuals most often contract their injury at a young age and are deemed to a life of more or less physical inactivity. In addition to the primary implications of the SCI, severe SCI individuals are stigmatized by conditions related to their physically inactive lifestyle. It is unknown if these inactivity related conditions are potentially reversible and the aim of the present study was, therefore, to examine the effect of exercise on SCI individuals. Ten such individuals (six with tetraplegia and four with paraplegia; age 27-45 years; time since injury 3-23 years) were exercise trained for 1 year using an electrically induced computerized feedback controlled cycle ergometer. They trained for up to three times week (mean 2.3 times), 30 min on each occasion. The gluteal, hamstring and quadriceps muscles were stimulated via lectrodes placed on the skin over their motor points. During lie first training bouts, a substantial variation in performance was seen between the subjects. A majority of them were capable of performing 30 min of exercise in the first bout, however, two individuals were only able to perform a few minutes of exercise. After training for 1 year all of the subjects were able to perform 30 min of continuous training and the work output had increased from 4±1 (mean±SE) to 17±2 kilo Joules per training bout (P<0.05). The maximal oxygen uptake during electrically induced exercise increased from 1.20±0.08 litres per minute measured after a few weeks habituation to the exercise to 1.43±0.09 litres per minute after training for 1 year (P<0.05). Magnetic resonance cross sectional images of the thigh were performed to estimate muscle mass and an increase of 12% (mean, P<0.05) was seen in response to 1 year of training. In biopsies taken before exercise various degrees of atrophy were observed in the individual muscle fibres, a phenomenon that was partially normalized in all subjects after training. The fibre type distribution in skeletal muscles is known to shift towards type IIB fibres (fast twitch, fast fatiguable, glycolytic fibres) within the first 2 years after the spinal cord injury. The muscle in the present investigation contained 63% of myosin heavy chain (MHQ isoform IIB, 33% MHC isoform IIA (fast twitch, fatigue resistant) and less than 5% MHC isoform I (slow twitch) before training. A shift towards more fatigue resistant contractile proteins was found after 1 year of training. The percentage of MHC isoform IIA increased to 61% of all contractile protein and a corresponding decrease to 32% was seen in the fast fatiguable MHC isoform IIB, where as MHC 1 only comprised 7% of the total amount of MHC. This shift was accompanied by a doubling of the enzymatic activity of citrate synthase, as an indicator of mitochondrial oxidative capacity. It is concluded that inactivity-associated changes in exercise perfomance capacity and skeletal muscle occurring in SCI individuals after injury are reversible, even up to over 20 years after the injury. It follows that electrically induced exercise training of the paralysed limbs is an effective rehabilitation tool that should be offered to SCI individuals in the future

Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells

A critical determinant of tumor eradication by adoptive immunotherapy is the tumor associated antigen recognized by cytotoxic T lymphocytes. Here the authors generate ex vivo autologous cytotoxic T lymphocytes by exposure to antigens induced by DNA demethylation and report the results of a phase 1 trial of 25 patients with recurrent glioblastoma multiforme with tumor regression in three patients

Major stroke in a 19-year-old patient with a univentricular heart

Patients with univentricular heart malformations are at increased risk of suffering from thromboembolic events. We present a case of a 19-year-old woman born with a univentricular heart who suffered a major stroke while being treated with only salicylic acid. At least 20% of patients with univentricular hearts have been reported to experience thromboembolic events, of which 25% are fatal. Despite the high incidence of thromboembolic events, no consensus has been reached regarding the role of long-term anti-thrombotic treatment in this group of patients. This lack of consensus warrants future studies that compare the different therapeutic strategies

Intra-arterial nimodipine for cerebral vasospasm after subarachnoid haemorrhage:Influence on clinical course and predictors of clinical outcome

Intra-arterial nimodipine (IAN) has shown a promising effect on cerebral vasospasm (CV) after aneurysmal subarachnoid haemorrhage. At our institution, Rigshospitalet, IAN treatment has been used since 2009, but the short- and long-term clinical efficacy of IAN has not yet been assessed. The purpose was to evaluate the efficacy and clinical outcome of IAN treatment of symptomatic CV, and to assess the predictors of clinical outcome. Medical records of 25 patients undergoing a total of 41 IAN treatment sessions were retrospectively reviewed. Data on angiographic results, blood-flow velocities and the clinical condition before and after the IAN treatment were recorded. Predictors of the clinical outcome were assessed with a linear regression model. Positive angiographic response was achieved in 95.1% of 41 IAN treatment sessions. Flow-velocity measurements showed no relationship with angiographic responses of IAN. The immediate clinical improvement was observed in three patients (12%). Five patients (20%) had a favourable outcome at discharge and at three-month follow-up; 10 patients (40%) had a moderate to poor outcome; and the rest (40%) died. Increased number of affected vessels and number of procedures carried out per patient, and a trend toward an increased delay time from symptomatic CV to confirming angiographic CV and thus instituting IAN treatment predicted the poor clinical outcome. IAN treatment appears to be effective in reversing angiographic CV. However, it is not always effective in reversing clinical deterioration, as several other factors including treatment delay affect the clinical course

Modified condylotomy versus conventional conservative treatment in painful reciprocal clicking-a preliminary prospective study in eight patients

Modified condylotomy may be relevant in severe painful reciprocal clicking of the temporomandibular joint (TMJ) where conservative treatment is insufficient. The effect of the modified condylotomy was analyzed and compared with conventional nonsurgical treatment in a randomized pilot study of eight patients, 19-44 years of age, with severe painful reciprocal clicking. Before and after treatment, assessments were performed by subjective reports, clinical recordings, and blinded evaluations of radiography and magnetic resonance imaging (MRI). Based on the clinical evaluations before treatment, all conditions were disc displacements with reduction and arthralgia (Research diagnostic criteria for temporomandibular disorders), but based on MRI, one patient had disc displacement without reduction and another had normal disc position. The treatment effect was significantly better and the disorders were significantly more reduced with condylotomy than with conventional nonsurgical treatment (P < 0.05, Mann-Whitney U test). In the surgical group, the clicking and locking had disappeared, the pain during function was significantly reduced (P < 0.05, Friedman ANOVA), and in two patients the disc position was normalized. The clicking still persisted in the nonsurgical patients and the disc position was unchanged. Our conclusion is that modified condylotomy is a promising option to reduce symptoms and signs in severe painful reciprocal clicking