Single sodium channels from human skeletal muscle in planar lipid bilayers: characterization and response to pentobarbital

PURPOSE: To investigate the response to general anesthetics of different sodium-channel subtypes, we examined the effects of pentobarbital, a close thiopental analogue, on single sodium channels from human skeletal muscle and compared them to existing data from human brain and human ventricular muscle channels. METHODS: Sodium channels from a preparation of human skeletal muscle were incorporated into planar lipid bilayers, and the steady-state behavior of single sodium channels and their response to pentobarbital was examined in the presence of batrachotoxin, a sodium-channel activator. Single-channel currents were recorded before and after the addition of pentobarbital (0.34-1.34 mM). RESULTS: In symmetrical 500 mM NaCl, human skeletal muscle sodium channels had an averaged single-channel conductance of 21.0 +/- 0.6 pS, and the channel fractional open time was 0.96 +/- 0.04. The activation midpoint potential was -96.2 +/- 1.6 mV. Extracellular tetrodotoxin blocked the channel with a half-maximal concentration (k1/2) of 60 nM at 0 mV. Pentobarbital reduced the time-averaged conductance of single skeletal muscle sodium channels in a concentration-dependent manner (inhibitory concentration 50% [IC50] = 0.66 mM). The steady-state activation was shifted to more hyperpolarized potentials (-16.7 mV at 0.67 mM pentobarbital). CONCLUSION: In the planar lipid bilayer system, skeletal muscle sodium channels have some electrophysiological properties that are significantly different compared with those of sodium channels from cardiac or from central nervous tissue. In contrast to the control data, these different human sodium channel subtypes showed the same qualitative and quantitative response to the general anesthetic pentobarbital. The implication of these effects for overall anesthesia will depend on the role the individual channels play within their neuronal networks, but suppression of both central nervous system and peripheral sodium channels may add to general anesthetic effect

Wel of geen gabapentinoïden bij volwassenen met chronische neuropathische pijn?

CASE DESCRIPTION: A frail 85-year-old woman with chronic neuropathic pain after hip surgery, not responding to treatment with acetaminophen and morphine patches. Should she be prescribed a gabapentinoid? DISCUSSION: Gabapentinoids and antidepressants are considered first-line therapies. They achieve clinically relevant (i.e. ≥ 50%) pain reduction in approximately one-third of patients with postherpetic neuralgia and peripheral diabetic neuropathy. Evidence for other types of neuropathic pain is limited. Adverse events occur frequently and are mostly mild in nature; serious adverse effects are rare. Prescription of gabapentinoids in specific patient groups (e.g. elderly patients and patients with a history of depression or substance abuse) deserves careful consideration, because the risk/benefit ratio in those groups may be altered. In order to reduce the risk of withdrawal symptoms, slow tapering is recommended. CONCLUSION: Chronic neuropathic pain often has a negative impact on the quality of life and is difficult to treat. In general, treatment with a gabapentinoid is a possible first-line treatment option. However, they may be relatively contraindicated in vulnerable patients

Wel of geen gabapentinoïden bij volwassenen met chronische neuropathische pijn?

CASE DESCRIPTION: A frail 85-year-old woman with chronic neuropathic pain after hip surgery, not responding to treatment with acetaminophen and morphine patches. Should she be prescribed a gabapentinoid? DISCUSSION: Gabapentinoids and antidepressants are considered first-line therapies. They achieve clinically relevant (i.e. ≥ 50%) pain reduction in approximately one-third of patients with postherpetic neuralgia and peripheral diabetic neuropathy. Evidence for other types of neuropathic pain is limited. Adverse events occur frequently and are mostly mild in nature; serious adverse effects are rare. Prescription of gabapentinoids in specific patient groups (e.g. elderly patients and patients with a history of depression or substance abuse) deserves careful consideration, because the risk/benefit ratio in those groups may be altered. In order to reduce the risk of withdrawal symptoms, slow tapering is recommended. CONCLUSION: Chronic neuropathic pain often has a negative impact on the quality of life and is difficult to treat. In general, treatment with a gabapentinoid is a possible first-line treatment option. However, they may be relatively contraindicated in vulnerable patients

Percutaneous fetoscopic patch closure of human spina bifida aperta: advances in fetal surgical techniques may obviate the need for early postnatal neurosurgical intervention

BACKGROUND: A percutaneous minimally invasive fetoscopic approach was attempted for closure of a spina bifida aperta in two fetuses with L5 lesions. The goal was to obviate the need for postnatal neurosurgery to manage this condition. METHODS AND RESULTS: The percutaneous fetoscopic procedures were performed by a two-layer approach at respectively 22+/-2 and 22+/-4 weeks of gestation. The fetuses were delivered respectively at 32+/-6 and 32+3 weeks of gestation. Their neural cords were completely covered although in small areas skin closure was incomplete. Postnatally, complete skin closure occurred beneath an occlusive draping within 2 to 3 weeks such that neurosurgical intervention was not required. Both neonates showed reversal of hindbrain herniation, near-normal leg function, and satisfactory bladder and bowel function. For one of the two fetuses, ventriculoperitoneal shunt insertion was not required. CONCLUSIONS: Percutaneous minimally invasive fetoscopic patch closure of spina bifida aperta offers a substantially less maternal trauma than open fetal surgical repair and currently may even obviate the need for postnatal neurosurgical repair. With a little further improvement in surgical techniques and a better understanding of incorporating surgical patches into the fetus, complete skin closure seems possible in the near futur

Percutaneous fetoscopic laser decompression of congenital high airway obstruction syndrome (CHAOS) from laryngeal atresia via a single trocar--current technical constraints and potential solutions for future interventions

OBJECTIVE: To alleviate congenital high airway obstruction syndrome (CHAOS) from laryngeal atresia by percutaneous minimally-invasive fetoscopic tracheal decompression using laser. METHODS: The procedure was performed via one trocar under general maternofetal anesthesia in a human fetus with CHAOS from laryngeal atresia at 21+6 weeks of gestation. RESULTS: Normalization of the lung-heart size relationship was observed within days after the procedure. The fetus was delivered by ex utero intrapartum treatment (EXIT) in order to perform a tracheotomy at 31+1 weeks of gestation and survived hospital treatment to discharge. CONCLUSIONS: Percutaneous minimally-invasive fetoscopic decompression of the fetal trachea via a single trocar is feasible in human fetuses with CHAOS from laryngeal atresi