Developmental regulation of the A-type potassium-channel current in hippocampal neurons: role of the Kvbeta 1.1 subunit.

The rapidly inactivating A-type K+ current (IA) is prominent in hippocampal neurons; and the speed of its inactivation may regulate electrical excitability. The auxiliary K+ channel subunit Kvbeta 1.1 confers fast inactivation to Shaker-related channels and is postulated to affect IA. Whole-cell patch clamp recordings of rat hippocampal pyramidal neurons in primary culture showed a developmental decrease in the time constant of inactivation (tau(in)) of voltage-gated K+ currents: 17.9+/-1.5 ms in young neurons (5-7 days in vitro; n=53, mean+/-S.E.M.); 9.9+/-1.0 ms in mature neurons (12-15 days in vitro; n=72, mean+/-S.E.M., P<0.01). During the same developmental time, the level of Kvbeta 1.1 transcript increased more than two-fold in vitro and in vivo, determined by semi-quantitative reverse transcriptase-polymerase chain reaction for hippocampus. The hypothesis that up-regulation of Kvbeta 1.1 led to the changes in tau(in) was tested in vitro, using antisense knockdown. Kvbeta 1.1-specific antisense DNA was introduced with a modified herpes virus co-expressing enhanced green fluorescent protein and knockdown of Kvbeta 1.1 was verified by immunocytochemistry. Following transduction with the antisense virus, mature neurons reverted to tau(in) values characteristic of young neurons: 18.3+/-2.4 ms (n=20). The effect of antisense knockdown on electrical excitability was tested using current-clamp protocols to induce repetitive firing. Treatment with the antisense virus increased the interspike interval over a range of membrane depolarization (baseline membrane potential=-40 to +20 mV). This effect was most pronounced at -40 mV, where the ISI of the first pair of action potentials was nearly doubled. These data indicate that Kvbeta 1.1 contributes to the developmental control of IA in hippocampal neurons and that the magnitude of effect is sufficient to regulate electrical excitability. Viral-mediated antisense knockdown of Kvbeta 1.1 is capable of decreasing the electrical excitability of post-mitotic hippocampal neurons, suggesting this approach has applicability to gene therapy of neurological diseases associated with hyperexcitability.

Physician self-referral and imaging use appropriateness: negative cervical spine MRI frequency as an assessment metric.

BACKGROUND AND PURPOSE: Imaging self-referral is increasingly cited as a contributor to diagnostic imaging overuse. The purpose of this study was to determine whether ownership of MR imaging equipment by ordering physicians influences the frequency of negative cervical spine MR imaging findings. MATERIALS AND METHODS: A retrospective review was performed of 500 consecutive cervical spine MRIs ordered by 2 separate referring-physician groups serving the same geographic community. The first group owned the scanners used and received technical fees for their use, while the second group did not. Final reports were reviewed, and for each group, the percentage of negative study findings and the frequency of abnormalities were calculated. The number of concomitant shoulder MRIs was recorded. RESULTS: Five hundred MRIs meeting inclusion criteria were reviewed (250 with financial interest, 250 with no financial interest). Three hundred fifty-two had negative findings (190 with financial interest, 162 with no financial interest); there were 17.3% more scans with negative findings in the financial interest group (P = .006). Among scans with positive findings, there was no significant difference in the mean number of lesions per scan, controlled for age (1.90 with financial interest, 2.19 with no financial interest; P = .23). Patients in the financial interest group were more likely to undergo concomitant shoulder MR imaging (24 with financial interest, 11 with no financial interest; P = .02). CONCLUSIONS: Cervical spine MRIs referred by physicians with a financial interest in the imaging equipment used were significantly more likely to have negative findings. There was otherwise a highly similar distribution and severity of disease between the 2 patient samples. Patients in the financial interest group were more likely to undergo concomitant shoulder MR imaging.

Trends in spinal pain management injections in academic radiology departments.

BACKGROUND AND PURPOSE: There is a paucity of information present in the current literature with regard to the role of SPMI performance in academic radiology centers. Our aim was to evaluate the current practice patterns for the performance of SPMIs in academic radiology departments. MATERIALS AND METHODS: A survey of 186 academic radiology departments in the United States was conducted between March 2009 and May 2009. The survey included questions on departmental demographics, recent trends in departmental SPMI performance, type of physicians who refer to radiology for SPMI performance, types of SPMIs offered, the fraction of total institutional SPMI volume performed by radiologists, and the current state of resident and fellow SPMI training proficiency. RESULTS: Forty-five of the 186 (21.4%) surveys were completed and returned. Twenty-eight of the 45 responding departments stated that they performed SPMIs; the other 17 stated that they did not. Among the 28 responding departments that perform SPMIs, 6 (21.4%), 5 (17.9%), and 8 (28.6%) stated that the number of departmental SPMIs had, respectively, increased, decreased, or remained stable during the past 5 years. SPMI referrals to radiology were made by orthopedic surgeons, neurologic surgeons, neurologists, psychiatrists, anesthesiologists, and internal medicine physicians. CESIs, SNRBs, facet injections, and synovial cyst aspirations are the most frequently performed injections. Fellows and residents become proficient in 88.5% and 51.9%, respectively, of SPMI-performing departments. Most departments perform <50% of the SPMI volume of their respective institutions. CONCLUSIONS: Most responding academic radiology departments perform SPMIs. Most fellows and just more than half of residents at SPMI-performing departments achieve SPMI proficiency. For the most part, the number of SPMIs performed in responding departments has been stable during the past 5 years.

CT fluoroscopy-guided cervical interlaminar steroid injections: safety, technique, and radiation dose parameters.

BACKGROUND AND PURPOSE: Cervical epidural steroid injections are approached with trepidation because of concerns over safety, including direct spinal cord injury. CT fluoroscopy is an alternative to conventional fluoroscopy that could potentially help reduce the risk of injury by providing improved localization of the needle tip. We sought to determine rates of technical success and risk of complications in our initial cohort of patients treated with cervical interlaminar ESI performed under CTF guidance. MATERIALS AND METHODS: In this retrospective case series, we reviewed procedural details and CTF images of 53 consecutive cervical interlaminar ESIs performed on 50 patients over a period of 8 months. Rates of technical success, incidence of complications, procedure times, and factors that influence radiation exposure were examined. RESULTS: No symptomatic procedural complications were observed. A single case of intrathecal contrast injection was observed, from which the patient was asymptomatic. The remaining injections were all technically successful. Injections were performed at every cervical level, as high as C1-C2. Total procedure times averaged less than 20 minutes. Average CT fluoroscopic time was 24 seconds and median tube current was 70 mA. CONCLUSIONS: CTF-guided cervical interlaminar ESI can be performed at all levels in the cervical spine with a low rate of procedural complications. Short total procedure times, CT-fluoroscopy times, and reduced tube current make this procedure a practical alternative to cervical ESI performed under conventional fluoroscopy.

Viral vector-mediated expression of K+ channels regulates electrical excitability in skeletal muscle.

Modification of K+ currents by exogenous gene expression may lead to therapeutic interventions in skeletal muscle diseases characterized by alterations in electrical excitability. In order to study the specific effects of increasing outward K+ currents, we expressed a modified voltage-dependent K+ channel in primary cultured rat skeletal muscle cells. The rat Kv1.4 channel was expressed as an N-terminal fusion protein containing a bioluminescent marker (green fluorescent protein). Transgene expression was carried out using the helper-dependent herpes simplex 1 amplicon system. Transduced myoballs, identified using fluorescein optics and studied electrophysiologically with single-cell patch clamp, exhibited a greater than two-fold increase in K+ conductance by 20-30 h after infection. This increase in K+ current led to a decrease in membrane resistance and a 10-fold increase in the current threshold for action potential generation. Electrical hyperexcitability induced by the Na+ channel toxin anemone toxin II (1 microM) was effectively counteracted by overexpression of Kv1.4 at 30-32 h after transduction. Thus, virally induced overexpression of a voltage-gated K+ channel in skeletal muscle has a powerful effect in reducing electrical excitability.