Reliability of perioperative SSEP recordings in spine surgery

OBJECTIVE: The reproducibility and clinical reliability of perioperative somatosensory-evoked potentials (SSEP) were prospectively evaluated in uneventful scoliosis surgery. The influence of anesthesia owing to induction of total intravenous anesthesia (TIVA) upon preoperative SSEP and the variability of intraoperative SSEP were calculated. The potential effect of spine surgery was assessed by comparing pre- to postoperative SSEP. METHODS: A total of 2,143 pre-, intra- and postoperative tibial and median SSEP recorded in 25 patients undergoing spine surgery owing to idiopathic scoliosis were analyzed. The anesthesia protocol consisted of a computerized target controlled infusion (TCI) device for propofol and intravenous application of an opioid. RESULTS: Anesthesia induced a significant and comparable prolongation of the tibial SSEP onset, P40 and P60 latencies, while the N50 latency was less changed. Throughout anesthesia, latencies of median (onset, N20, P25 and N35) and tibial (onset, P40, N50 and P60) SSEP showed mean variations of less than 6%. The intraoperative SSEP amplitudes were less stable with a relative standard deviation of 30-40%. In uneventful spine surgery, the postoperative tibial SSEP were not significantly changed in comparison to preoperative recordings. CONCLUSIONS: By using a standardized anesthesia protocol, the impact of anesthesia on preoperative SSEP can be predicted. Furthermore, the controlled application of sedatives and analgesics allows recording of stable SSEP parameters for intraoperative monitoring purposes. As in uneventful spine surgery pre- to postoperative SSEP are unchanged the latter comparison can be applied as an additional perioperative neuromonitoring procedure to assess the influence of spine surgery or other invasive interventions on spinal cord function.     

Simulation tool for schedule-dependent etoposide exposure based on pharmacokinetic findings published in the literature

It is the aim of this study to establish a simulation tool for etoposide (Eto) which can be used to interpret drug monitoring data in clinical practice and to design new schedules for future protocols. As schedule dependency was observed for Eto, knowledge of concentration-time profiles is important. Pharmacokinetic data from children after low-dose i.v. administration of Eto together with data reported in the literature were used to construct the simulation tool. Validation was performed by independently reproducing various published data. Dose linearity of AUC was shown over the whole dose range of 20-2000 mg/m2 reported in the literature and fits the predictions by the simulation tool. There was no difference in clearance between children and adults. Close agreement was found between predicted and reported concentration-time profiles after various administration schedules. However, subgroups with significantly altered pharmacokinetics of Eto, such as patients with renal impairment or concurrent cisplatin chemotherapy, were excluded from the comparisons. In these patients values predicted for a 'regular' patient might be used as a base for possible dose modifications. In summary, a pharmacokinetic model of high predictive value is presented which allows simulations of Eto concentration-time profiles for low- as well as high-dose conditions and various infusion times.     

MR morphology of alar ligaments and occipitoatlantoaxial joints: study in 50 asymptomatic subjects

PURPOSE: To assess the magnetic resonance (MR) imaging appearance of the alar ligaments and joints in the upper cervical spine to determine the prevalence of structural alterations in asymptomatic individuals. MATERIALS AND METHODS: Fifty healthy individuals (31 men, 19 women) with a mean age of 30 years (range, 19-47 years) underwent coronal T1- and T2-weighted and transverse T1-weighted MR imaging. MR findings were analyzed independently by two musculoskeletal radiologists, with disagreements resolved in conference. RESULTS: Alar ligaments were detected in 42 (84%) (left side) and 38 (76%) (right side) of 50 individuals. The majority of ligaments (88%) and joints (58%) of the craniocervical junction (CCJ) were asymmetric. Asymmetry of the joint between C1 and C2 was less frequent (46%). Small amounts of fluid were detected in 8% of CCJ joints and 56% of C1-C2 joints in asymptomatic individuals. CONCLUSION: Asymmetry of alar ligaments, CCJ and C1-C2 facet joints, and joint effusions are common in asymptomatic individuals. The clinical relevance of these MR findings is therefore limited in the identification of the source of neck pain in symptomatic patients.     

Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A

Plasma membrane GABA transporters participate in neural signaling through re-uptake of neurotransmitter. The domains of the transporter that mediate GABA translocation and regulate transport are not well understood. In the present experiments, the N-terminal cytoplasmic domain of the GABA transporter GAT1 regulated substrate transport rates. This domain directly interacted with syntaxin 1A, a SNARE protein involved in both neurotransmitter release and modulation of calcium channels and cystic fibrosis transmembrane regulator (CFTR) chloride channels. The interaction resulted in a decrease in transporter transport rates. These data demonstrate that intracellular domains of the GABA and protein-protein interactions regulate substrate translocation, and identify a direct link between the machinery involved in transmitter release and re-uptake.     

All-trans-retinoic acid increases cytosine arabinoside cytotoxicity in HL-60 human leukemia cells in spite of decreased cellular ara-CTP accumulation

Background: Accumulation of the cytosine arabinoside (ara-C) metabolite ara-C-triphosphate (ara-CTP) in leukemic blast cells is considered to be the main determinant of ara-C cytotoxicity in vitro and in vivo. Retinoids such as all-trans-retinoic acid (ATRA) have been shown to increase the sensitivity of acute myelogenous leukemic (AML) blast cells to ara-C. To investigate the mechanism of this sensitisation, the hypothesis was tested that ATRA augments cellular ara-CTP levels in human-derived myelogenous leukemia HL-60 cells.Materials and methods: The effect of ATRA and 13-cis-retinoic acid on ara-CTP accumulation and ara-C-induced apoptosis was studied. Ara-CTP levels were measured by high-performance liquid chromatography (HPLC), cytotoxicity by the tetrazolium (MTT) assay, and apoptosis by occurrence of DNA fragmentation (gel electrophoresis), cell shrinkage and DNA loss (flow cytometry).Results: Pretreatment of HL-60 cells with ATRA (0.01–1 µM) caused a significant decrease in intracellular ara-CTP levels; e.g., incubation for 72 hours with ATRA 1 µM prior to one hour ara-C 10 µM reduced ara-CTP levels to 41% ± 4% of control. Similar results were obtained after preincubation with 13-cis-retinoic acid. In spite of decreased ara-CTP levels, the cytotoxicity of the combination was supraadditive and ATRA augmented ara-C-induced apoptosis.Conclusions: At therapeutically relevant concentrations ATRA increased ara-C cytotoxicity and ara-C induced apoptosis but this augmentation is not the corollary of elevated ara-CTP levels. The feasibility of ara-C treatment optimisation via strategies other than those involving elevation of ara-CTP levels should be investigated further.     

Evaluation of the Sheffield system for identifying children at risk from unexpected death in infancy. Results from Birmingham and Newcastle upon Tyne

The "at birth" system which is used in Sheffield to identify children likely to die unexpectedly in infancy, was tested retrospectively in Birmingham (83 cases) and in Newcastle upon Tyne (56 cases). The discrimination between cases and age-matched controls was poor in both cities. Analysis of the 8 factors used in the system showed that only 2 maintained significant case/control differences in Birmingham and Newcastle. Further investigation showed that other factors from maternity records showed significant case/control differences in these cities. Although the system used in Sheffield would not be of use in a prospective prevention programme in either Newcastle or Birmingham, the possibility of evolving an "at risk" system which might apply more widely is discussed.     

Phase-contrast MR angiography of peripheral arteries: technique and clinical application

This articles describes Phase-Contrast-MRA (PC-MRA) techniques and their current clinical applications for peripheral arteries based on more than 250 clinical MRA studies performed at two institutions. PC-MRA depends on phase shifts caused by blood flow and thus this technique permits the use of coronal or sagittal slice orientations with large FOV's along the direction of the vessel of interest. Clinical applications focus on patients with peripheral arterial occlusive disease (PAOD) describing the role and limitations of PC-MRA for the work-up of stenoses, occlusions, aneurysms, and postsurgical follow-up. Recommendations for clinical routine are provided. A combined MR angiographic approach with various MRA techniques depending on the vessel segment to be imaged, PC-flow velocity measurements, and high-resolution scans of the vessel wall may turn out to be diagnostically effective and provide a comprehensive test for PAOD within the near future. Received: 30 January 1998; Revision received: 17 April 1998; Accepted: 6 May 1998