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1.
Hum Gene Ther ; 26(9): 614-21, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25953425

RESUMO

We evaluated safety and feasibility of high-pressure transvenous limb perfusion in an upper extremity of adult patients with muscular dystrophy, after completing a similar study in a lower extremity. A dose escalation study of single-limb perfusion with 0.9% saline was carried out in nine adults with muscular dystrophies under intravenous analgesia. Our study demonstrates that it is feasible and definitely safe to perform high-pressure transvenous perfusion with 0.9% saline up to 35% of limb volume in the upper extremities of young adults with muscular dystrophy. Perfusion at 40% limb volume is associated with short-lived physiological changes in peripheral nerves without clinical correlates in one subject. This study provides the basis for a phase 1/2 clinical trial using pressurized transvenous delivery into upper limbs of nonambulatory patients with Duchenne muscular dystrophy. Furthermore, our results are applicable to other conditions such as limb girdle muscular dystrophy as a method for delivering regional macromolecular therapeutics in high dose to skeletal muscles of the upper extremity.


Assuntos
Distrofia Muscular de Duchenne/terapia , Cloreto de Sódio/administração & dosagem , Adulto , Feminino , Técnicas de Transferência de Genes , Terapia Genética , Humanos , Masculino , Pessoa de Meia-Idade , Perfusão , Pressão , Resultado do Tratamento , Adulto Jovem
2.
Mol Ther ; 20(2): 456-61, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21772257

RESUMO

We evaluated safety and feasibility of the transvenous limb perfusion gene delivery method in muscular dystrophy. A dose escalation study of single limb perfusion with 0.9% saline starting with 5% of limb volume was carried out in adults with muscular dystrophies under intravenous analgesia/anesthesia. Cardiac, vascular, renal, muscle, and nerve functions were monitored. A tourniquet was placed above the knee with inflated pressure of 310 mm Hg. Infusion was carried out with a clinically approved infuser via an intravenous catheter inserted in the saphenous vein with a goal infusion rate of 80 ml/minute. Infusion volume was escalated stepwise to 20% limb volume in seven subjects. No subject complained of any post procedure pain other than due to needle punctures. Safety warning boundaries were exceeded only for transient depression of limb tissue oximetry and transient elevation of muscle compartment pressures; these were not associated with nerve, muscle, or vascular damage. Muscle magnetic resonant imaging (MRI) demonstrated fluid accumulation in muscles of the perfused lower extremity. High-pressure retrograde transvenous limb perfusion with saline up to 20% of limb volume at above infusion parameters is safe and feasible in adult human muscular dystrophy. This study will serve as a basis for future gene transfer clinical trials.


Assuntos
Extremidade Inferior , Distrofias Musculares/terapia , Perfusão/métodos , Cloreto de Sódio/administração & dosagem , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Músculo Esquelético/metabolismo , Distrofias Musculares/diagnóstico , Consumo de Oxigênio , Perfusão/efeitos adversos , Pressão , Adulto Jovem
6.
Paediatr Anaesth ; 18(7): 642-4, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18422882

RESUMO

BACKGROUND: Forced-air warming systems have proven effective in preventing perioperative hypothermia. To date, reported adverse events relate primarily to overheating and thermal injuries. This study uses a simple model to show that forced-air warming blankets become ineffective if they get wet. METHODS: Temperature sensor probes were inserted into three 1-liter fluid bags. Group C bags served as the control. Groups D (dry) and W (wet) bags were placed on Bair Hugger(R) Model 555 (Arizant Healthcare, Inc., Eden Prairie, MN, USA) pediatric underbody blankets. The warming blanket for Group W bags was subsequently wet with irrigation fluid. Temperature was documented every 5 min. This model was repeated two times for a total of three cycles. Statistical analysis was performed using anova for repeated measures. RESULTS: Starting temperatures for each model were within a 0.3 degrees C range. Group C demonstrated a steady decline in temperature. Group D maintained and slightly increased in temperature during the observation period, while Group W exhibited a decrease in temperature at a rate similar to Group C. These results were significant at P < 0.005. CONCLUSIONS: A wet forced-air warming blanket is ineffective at maintaining normothermia. Once wet, the warming blanket resulted in cooling similar to the control group.


Assuntos
Roupas de Cama, Mesa e Banho , Hipotermia/prevenção & controle , Reaquecimento/instrumentação , Água/efeitos adversos , Roupas de Cama, Mesa e Banho/efeitos adversos , Desenho de Equipamento , Falha de Equipamento , Modelos Biológicos , Reaquecimento/efeitos adversos , Temperatura , Fatores de Tempo
8.
Anesth Analg ; 100(6): 1797-1803, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15920216

RESUMO

In this study, we compared the effect of isoflurane and desflurane on the posterior tibial somatosensory evoked potential recorded by scalp electrodes during correction of idiopathic scoliosis in pediatric patients. Depth of sedation was controlled by maintaining bispectral index (BIS) at 60 throughout the study. Comparison of patients breathing desflurane and isoflurane showed an evoked cortical amplitude (N37-P45) of 0.53 +/- 0.3 microV versus 1.3 +/- 0.8 microV (P = 0.014), respectively. In addition to this comparison, a crossover design was included whereby the desflurane or isoflurane received in the first part of the study was changed to the other anesthetic. Substituting one anesthetic for another confirmed our initial finding that the cortical evoked amplitude is greater with isoflurane than with desflurane. No differential effect was found between desflurane and isoflurane on the evoked subcortical (N31-P34) amplitude or the P37 latency.


Assuntos
Anestesia por Inalação , Anestésicos Inalatórios , Eletroencefalografia/efeitos dos fármacos , Potenciais Somatossensoriais Evocados/efeitos dos fármacos , Isoflurano , Isoflurano/análogos & derivados , Procedimentos Ortopédicos , Escoliose/cirurgia , Adolescente , Anestésicos Inalatórios/administração & dosagem , Temperatura Corporal/efeitos dos fármacos , Criança , Pré-Escolar , Estudos Cross-Over , Desflurano , Estimulação Elétrica , Feminino , Hemodinâmica , Humanos , Isoflurano/administração & dosagem , Masculino , Monitorização Intraoperatória , Estudos Prospectivos , Nervo Tibial/fisiologia
9.
Anesth Analg ; 96(5): 1320-1324, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12707126

RESUMO

UNLABELLED: In this study, we examined the emergence characteristics of children tracheally extubated while deeply anesthetized with desflurane (Group D) or sevoflurane (Group S). Forty-eight children were randomly assigned to one of the two groups. At the end of the operation, all subjects were tracheally extubated while breathing 1.5 times the minimal effective concentration of assigned inhaled anesthetic. Recovery characteristics and complications were noted. Group D patients had higher arousal scores on arrival to the postanesthesia care unit than Group S patients. Later arousal scores were not significantly different. No serious complications occurred in either group. Coughing episodes and the overall incidence of complications after extubation were more frequent in Group D. Readiness for discharge and actual time to discharge were not significantly different between groups. Emergence agitation was common in both groups (33% overall, 46% for Group D, and 21% for Group S). Narcotic administration in the postanesthesia care unit occurred more frequently in Group D (10 of 24 patients) versus Group S (3 of 24 patients). Premedication with oral midazolam resulted in significantly longer emergence times regardless of the potent inhaled anesthetic administered. IMPLICATIONS: Deep extubation of children can be performed safely with desflurane or sevoflurane. Airway problems occur more frequently with desflurane. Awakening occurs more quickly with desflurane. Midazolam premedication has a greater effect on emergence times than does the choice of inhaled anesthetic. Emergence agitation occurs frequently with either technique.


Assuntos
Anestesia por Inalação , Anestésicos Inalatórios , Intubação Intratraqueal , Isoflurano , Isoflurano/análogos & derivados , Éteres Metílicos , Adolescente , Período de Recuperação da Anestesia , Anestesia por Inalação/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Nível de Alerta , Criança , Pré-Escolar , Desflurano , Feminino , Humanos , Lactente , Intubação Intratraqueal/efeitos adversos , Isoflurano/efeitos adversos , Laringismo/epidemiologia , Laringismo/etiologia , Masculino , Éteres Metílicos/efeitos adversos , Náusea e Vômito Pós-Operatórios/epidemiologia , Medicação Pré-Anestésica , Sevoflurano
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