Clinical evaluation of a lumbar interspinous dynamic stabilization device (the Wallis system) with a 13-year mean follow-up

The authors determined current health status of patients who had been included in a long-term survivorship analysis of a lumbar dynamic stabilizer. Among 133 living patients, 107 (average age at surgery, 44.2 ± 9.9 years) completed health questionnaires. All patients had initially been scheduled for decompression and fusion for canal stenosis, herniated disc, or both. In 20 patients, the implant was removed, and fusion was performed. The other 87 still had the dynamic stabilizer. Satisfaction, Oswestry disability index, visual analog scales for back and leg pain, short-form (SF-36) quality-of-life physical composite score, physical function, and social function were significantly better (p ≤ 0.05) in the patients who still had the dynamic stabilization device. SF-36 scores of the fused subgroup were no worse than those reported elsewhere in patients who had primary pedicle-screw enhanced lumbar fusion. This anatomy-sparing device provided a good 13-year clinical outcome and obviated arthrodesis in 80% of patients. All index operations were performed in the Unité de Pathologie Rachidienne, Centre Hospitalier Pellegrin, Bordeaux.     

Nanotechnologies: from information sciences to pharmacology

The considerable breakthroughs of the physics during the last 30 years allowed us to conceive components, devices or materials at the nanoscale level and to manipulate them. Applications are already envisaged in the field of the medical and pharmaceutical sciences. These nanotechnologies will be applied to the biology as well as the diagnosis, the therapeutics and the functional rehabilitation (nanomedicine). Consequences in the pharmaceutical research and development are also possible in a near future.     

Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness

Hyperkalemic periodic paralysis (HyperKPP) produces myotonia and attacks of muscle weakness triggered by rest after exercise or by K+ ingestion. We introduced a missense substitution corresponding to a human familial HyperKPP mutation (Met1592Val) into the mouse gene encoding the skeletal muscle voltage-gated Na+ channel NaV1.4. Mice heterozygous for this mutation exhibited prominent myotonia at rest and muscle fiber-type switching to a more oxidative phenotype compared with controls. Isolated mutant extensor digitorum longus muscles were abnormally sensitive to the Na+/K+ pump inhibitor ouabain and exhibited age-dependent changes, including delayed relaxation and altered generation of tetanic force. Moreover, rapid and sustained weakness of isolated mutant muscles was induced when the extracellular K+ concentration was increased from 4 mM to 10 mM, a level observed in the muscle interstitium of humans during exercise. Mutant muscle recovered from stimulation-induced fatigue more slowly than did control muscle, and the extent of recovery was decreased in the presence of high extracellular K+ levels. These findings demonstrate that expression of the Met1592ValNa+ channel in mouse muscle is sufficient to produce important features of HyperKPP, including myotonia, K+-sensitive paralysis, and susceptibility to delayed weakness during recovery from fatigue.     

Novel chloride channel mutations leading to mild myotonia among Chinese

We describe two Chinese families with a mild form of the myotonia congenita due to novel chloride channel (ClCN1) mutations. In one case, heterozygous I553F and H555N mutations were found. The patient shared the I553F mutation with his healthy father, and his mother had a history of mild myotonia when she was younger. In another family, autosomal dominant myotonia congenita was due to a L844F change. The physiological effects of the mutations were examined by using the two-electrode voltage-clamp technique after expression of the channels in Xenopus oocytes. All mutations drastically shifted the voltage required for half-maximal activation, more under conditions mimicking the homozygous situation, than under conditions mimicking the heterozygous situation. The larger effect was seen in the compound heterozygous situation combining the I553F and the H555N mutations. Our data suggest that myotonia congenita caused by CLCN1 mutations in Chinese have similar variable features to those found in the West.     

Vasoactive intestinal peptide-induced neuritogenesis in neuroblastoma SH-SY5Y cells involves SNAP-25

Vasoactive intestinal peptide (VIP) is a neuropeptide known to regulate proliferation and differentiation in normal and tumoral cells. We previously reported that VIP induced neuritogenesis in human neuroblastoma SH-SY5Y cells cultured in serum-free medium. This neuritogenesis was associated with a regulated expression of neuronal cytoskeleton markers. To further characterize the neuroblastic cell differentiation induced by VIP in human SH-SY5Y cells, we investigated expression of synaptosomal-associated protein of 25 kDa (SNAP-25), a protein implicated in exocytosis associated with different processes, including neurite outgrowth. Western immunoblotting and real-time RT-PCR analyses revealed that VIP increased expression of the SNAP-25 protein and the level of both SNAP-25a and SNAP-25b mRNA isoforms. Immunofluorescence experiments indicated that SNAP-25 was mainly located in neurites and at the plasma membrane in SH-SY5Y cells treated with VIP. RNA interference experiments demonstrated that SNAP-25 was involved in VIP-induced neuritogenesis. In conclusion, SNAP-25 is up-regulated and implicated in neuritogenesis in human neuroblastoma SH-SY5Y cells treated with the neuropeptide VIP.     

Synaptogenesis in the cerebellar cortex: differential regulation of gephyrin and GABAA receptors at somatic and dendritic synapses of Purkinje cells

In rodent cerebellar cortex, synaptogenesis occurs entirely postnatally, allowing study of the mechanisms of synapse formation in vivo. Here we monitored the clustering of GABA(A) receptors and the scaffolding protein gephyrin at GABAergic postsynaptic sites during rat cerebellar development. We found that GABA(A) receptors and gephyrin co-aggregate at nascent synapses in the molecular and Purkinje cell layers with a similar time course. With few exceptions, gephyrin and GABA(A) receptor subunits clustered selectively in front of presynaptic boutons expressing the vesicular inhibitory amino acid transporter VIAAT and no ectopic localization of these molecules was observed. Surprisingly, gephyrin clusters outlining the cell body of Purkinje cells were transient, and disappeared rapidly at the end of the second postnatal week. The loss of gephyrin from perisomatic synapses was coincident with a significant reduction in the size of GABA(A) receptor clusters. Furthermore, these changes were accompanied by a developmental decrease in the size of synaptic appositions, as documented by electron microscopy. These findings suggest that gephyrin takes part in the initial assembly of postsynaptic specializations and reveal an unsuspected heterogeneity in the molecular organization of the postsynaptic apparatus at somatic and dendritic synapses of mature Purkinje cells.     

Estradiol, testosterone, differential association and aggressive and non-aggressive risk-taking in adolescent girls

Although the relation between androgens and adolescent risk-taking has been relatively well documented in boys, little is known as to how sex steroid hormones relate to aggressive (ART) and/or non-aggressive adolescent risk-taking (NART) behavior in girls. On the basis of a sample of 298 adolescent girls (mean age: 14.3 years), we examined: (i) the relationship between serum levels of testosterone (T) and estradiol (E2) in relation to ART and NART and (ii) if differential association--having friends who are highly involved in risk-taking--moderates the relationship between relationships between hormones and risk-taking. The sample provided evidence of an association between free estradiol (FE2) and both NART (Beta=0.19; p<0.01) and ART (Beta=0.19; p<0.01), controlling for age and pubertal development. No relationship between T and ART or NART was found. The importance of the relationship between E2 and ART and NART differed between girls at different phases of their menstrual cycle and was significant only for girls in the mid-phase of the menstrual cycle. In addition, significant interactions between differential association and FE2 were found indicating that the relationship between FE2 and NART and ART was particularly strong in girls with high levels of differential association.     

Contributions of anesthesiology to the surgical treatment of cerebrovascular disease: the role of Arthur S. Keats, M.D

Increased tolerance to cerebral ischemia produced by general anesthesia during temporary carotid occlusion. By B. A. Wells, A. S. Keats, and D. A. Cooley. Surgery 1963; 54:216-23. Local anesthesia with little or no preoperative sedation is currently recommended as the anesthetic of choice for temporary carotid occlusion during carotid endarterectomy. Purported advantages include minimal circulatory and respiratory changes from the local anesthetic, and constant verbal contact can be maintained with the patient so that neurologic changes are promptly recognized. However, local anesthesia may not be satisfactory in uncooperative or semiconscious patients. We therefore undertook a trial of general anesthesia in 56 consecutive patients undergoing carotid endarterectomy. Patients were induced in standardized fashion using intravenous thiopental (100-400 mg), atropine (0.2 mg), and succinylcholine (40-80 mg). Cyclopropane, along with deliberate hypercapnia and hypertension, was used for anesthesia maintenance. All patients tolerated carotid occlusion for periods of up to 30 min during general anesthesia without shunt, bypass, or hypothermia. Except for one patient, electroencephalogram evidence of cerebral ischemia was not apparent during occlusion, and no patient suffered postoperative neurologic sequela. Twenty percent of patients who had their carotid arteries occluded preoperatively for 30-60 s without general anesthesia suffered convulsions. These data suggest that general anesthesia increased the tolerance to cerebral ischemia. Potential mechanisms involved might include: 1) decreased cerebral metabolic rate for oxygen; 2) increased cerebral blood flow from hypercapnia; 3) increased arterial oxygen tension; and 4) recruitment of new routes of collateral circulation.