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Biomedical subjects

J K Webb

Publications and source records attributed to J K Webb.

At least 37 records · Page 2Linked to original sources
PubMed2002

Spine-rib rotation differences at the apex in preoperative patients with adolescent idiopathic scoliosis: evaluation of a three-level ultrasound method.

This paper evaluates a new real-time ultrasound method to assess the difference between axial spinal (laminal) rotation and rib rotation at the apex of the scoliosis curve. An Aloka SSD 500 portable ultrasound machine with a veterinary long (172mm) 3.5 MHz linear array transducer was used to assess the reproducibility of the method in 13 preoperative patients with AIS. With the subject in a prone position and her head supported, readings of laminal and rib rotation were made directly on the back at 18 and 12 levels respectively The subject was repositioned after walking around the room and a second set of spinal and rib rotations obtained (repeats). All the readings were made by one observer (ASK). After plotting on graphs three levels of maximal difference between spine rotation and rib rotation about the apex were chosen visually by one observer (RGB) for which the mean apical spine-minus-rib rotation difference (SRRD) was calculated for each repeat. Findings for apical SRRDs. The mean apical SRRDs for the two repeats are 7.1 degrees and 6.9 degrees (range 2-18 degrees) with coefficients of variation of 49% and 62% respectively. Reproducibility. Graphic representation of spinal and rib rotation by 12 levels shows a fairly good agreement between repeats for most subjects. Spinal rotation is always greater than rib rotation. A paired t-test for the mean apical SRRD of the repeats shows no significant difference. Linear regression analysis of the mean apical SRRD repeats correlate significantly (r=0.70, P=0.008) with a residual mean square of 6.9 degrees (rms = 2.6 degrees). The technical error of the measurement (TEM) is 2.3 degrees and coefficient of reliability (R) 0.66. Conclusions. Real-time ultrasound can assess the difference between spinal and rib rotation about the apex of the scoliosis curve without the altered position detectably affecting the findings. The error (2-3 degrees) is high relative the mean apical SRRD (6-7 degrees). The apical SRRD findings have relevance to the pathogenesis of AIS.

Adolescent↗
PubMed2002

Preliminary study of a new real-time ultrasound method for measuring spinal and rib rotation in preoperative patients with adolescent idiopathic scoliosis.

A portable ultrasound machine with a linear array transducer was used by one observer (ASK) to evaluate the reproducibility for each of spinal (laminal) rotation and rib rotation in 13 preoperative patients with AIS (thoracic 7, thoracolumbar 6, mean Cobb angle 50 degrees, right 9, left 4, age 15.4 years, girls 10). With the subject in a prone position and her head supported, readings of spinal (laminal) and rib rotations were made directly on the back at 18 and 12 levels respectively. The subject was repositioned after walking around the room and a second set of spinal and rib rotations obtained (repeats). Conclusious. Repositioning the patient significantly alters some single level readings of lam inal rotation and rib rotation. Although the mean average spinal rotation and rib rotation each have acceptable reproducibility, repositioning the patient significantly alters the findings. In the appraisal of surgery by ultrasound the positional change reported here for (I) single level laminal rotation and rib rotation, and (2) mean average rotation imposes caution on the interpretation of the findings. The method enables the axial spine-nh rotation differences to be evaluated which is the subject of a separate paper.

Adolescent↗
PubMed2002

Anterior universal spine system for adolescent idiopathic scoliosis: a follow-up study using scoliometer, real-time ultrasound and radiographs.

Nine patients with AIS treated surgically with anterior USS instrumentation were examined by several methods pre-operatively and at each of 8 weeks, 1 year and 2 years after surgery (mean age 14.6 years, girls 7, boys 2, thoracolumbar 7, lumbar 1, thoracic 1, left 7, right 2). The methods used were (1) Scoliometer to measure angle of trunk inclinations (ATIs) in the standing forward bending position at each of 10 levels and converted to 18 levels by a computer program, (2) real-time ultrasound in the prone position of laminal rotations at each of 1 8 levels from TI-SI, and (3) anteroposterior radiographs in the standing erect position measured for each of Cobb angle, segmental vertebral rotation (Perdriolle) and segmental vertebral translation from the Ti-Si line (horizontal translation of each vertebral centroid from the T1-S1 line). The findings were plotted graphically and segmentally for each of Scoliometer ATJs, ultrasound laminal rotations, and radiographic vertebral rotations and translations. Findings. Graphical representation of the data shows that the improvement brought about by surgery is most clearly and consistently evident for segmental vertebral translation. The statistical analysis shows that the radiological parameters (Cobb angle, apical vertebral rotation and apical vertebral translation) and ultrasound spinal (laminal) rotation do not change detectably in follow-up. The Scoliometer ATI findings show an increase from 4 degrees (at 8 weeks) to 7 degrees (at 2 years) which is statistically significant. The evidence from this small sample of patients is consistent with the view that the compared with posterior USS, anterior USS surgery for AIS results in (1) similar initial rib hump correction, and (2) less rib hump reassertion during follow-up. More data are needed to evaluate these views.

Adolescent↗
PubMed2001

Changes in surface and radiographic deformity after Universal Spine System for right thoracic adolescent idiopathic scoliosis: is rib-hump reassertion a mechanical problem of the thoracic cage rather than an effect of relative anterior spinal overgrowth?

STUDY DESIGN: Analysis of preoperative, 8-week, 1-year, and 2-year data from patients with right thoracic adolescent idiopathic scoliosis treated by posterior Universal Spine System (Stratec Medical, Oberdorf, Switzerland). OBJECTIVE: Report 2-year results and the association between back surface and radiographic assessments. SUMMARY OF BACKGROUND DATA: Few longitudinal studies have related surface and radiographic data in the follow-up of surgical patients. METHODS: Of 34 patients with right thoracic adolescent idiopathic scoliosis having posterior Universal Spine System instrumentation, 27 had complete prospective back surface and radiographic appraisal. RESULTS: Cobb angle corrected from 58 degrees to 34 degrees (41%), apical vertebral rotation from 26 degrees to 20 degrees (23%), apical vertebral translation from 4.5 to 2.4 cm (47%), and maximum angle of trunk inclination from 17 degrees to 13 degrees (22%) (preoperative to 2 years). Rib-hump reassertion occurred between 8 weeks and 1 year, regardless of age, and correlated with changes in vertebral translation (for 10 vertebral levels corresponding to 10 back surface levels between C7 and S1, P = 0.001 MANOVA). Preoperative frontal tilt of L1 with concave fifth rib-spinal angle predicted the percentage correction of maximum angle of trunk inclination, and the concave ninth rib-spinal angle predicted reassertion of maximum angle of trunk inclination. CONCLUSIONS: Almost half of initial back surface correction is lost by 2 years. Segmental vertebral translation measurements most strongly correlate with segmental angle of trunk inclination measurements during follow-up. Rib-hump reassertion is best explained by unwinding of the thoracic cage tensioned by surgery rather than through relative anterior spinal overgrowth. Spine and thoracic cage factors determine rib-hump correction, so surgical disruption of the latter by costoplasty may prevent rib-hump reassertion. Results of scoliosis surgery should include surface data.

Adolescent↗
PubMed2001

Further evidence for cosmological evolution of the fine structure constant.

We describe the results of a search for time variability of the fine structure constant alpha using absorption systems in the spectra of distant quasars. Three large optical data sets and two 21 cm and mm absorption systems provide four independent samples, spanning approximately 23% to 87% of the age of the universe. Each sample yields a smaller alpha in the past and the optical sample shows a 4 sigma deviation: Delta alpha/alpha = -0.72+/-0.18 x 10(-5) over the redshift range 0.5<z<3.5. We find no systematic effects which can explain our results. The only potentially significant systematic effects push Delta alpha/alpha towards positive values; i.e., our results would become more significant were we to correct for them.

Journal Article↗
PubMed2001

Flexion osteotomy of the cervical spine: a new technique for correction of iatrogenic extension deformity in ankylosing spondylitis.

STUDY DESIGN: A new surgical technique of cervical osteotomy to correct an extension deformity of the cervical spine is described, and a case is reported. OBJECTIVES: To emphasize the disparate effect of osteotomy level on sagittal balance and gaze angle in surgical correction of global kyphotic deformity, and to describe a new surgical technique. SUMMARY OF BACKGROUND DATA: Previous reports of cervical osteotomy essentially have described extension osteotomy for correction of severe flexion deformity. To the authors' knowledge, flexion osteotomy to correct extension deformity of the cervical spine has not been described previously. METHODS: A 44-year-old woman with global kyphotic deformity caused by ankylosing spondylitis underwent corrective lumbar osteotomy at another institution. Ten years later, she experienced further development of the kyphosis, predominantly at the thoracic level, with resultant restriction of forward gaze. Thoracic corrective osteotomy was performed, which resulted in an upward deviation of her visual field. A flexion osteotomy was performed at C7-T1, using two separate posterior and anterior approaches, in one-stage, in the lateral decubitus. The use of transparent drapes permitted direct visualization of the chin-brow angle during operation. Anterior plate fixation prevented any translation at the osteotomy site. RESULTS: The osteotomy united; the gaze angle was fully corrected (45 degrees to -30 degrees ). No deterioration was noted at 2-year follow-up. CONCLUSIONS: Osteotomy at a higher level in the spine for correction of global kyphotic deformity may result in a significant overcorrection of the gaze angle upward. The authors believe that the new technique described in this report is a technically demanding but adequate and safe approach for correcting such a rare deformity.

Cervical Vertebrae↗
PubMed2001

Intraoperative motor evoked potentials to transcranial electrical stimulation during two anaesthetic regimens.

OBJECTIVES: To study motor evoked potentials (MEPs) to multi-pulse transcranial electrical stimulation (MP-TES) during orthopaedic spinal surgery under different anaesthetic regimens. METHODS: MEPs to MP-TES were recorded from tibialis anterior and abductor hallucis bilaterally in 50 operations. Anaesthesia was maintained with propofol and nitrous oxide in 29 operations and isoflurane (0.78+/-0.17% end-tidal) and nitrous oxide in 23 (two patients received both regimens). Analgesia was provided with fentanyl or remifentanil. RESULTS: Motor stimulation caused neither EEG changes nor seizures. MEPs were obtained in 97% of patients during propofol anaesthesia. The median amplitude and coefficient of variation (CV) at baseline (across all muscles) were 198 microV and 22%, respectively. Amplitudes throughout the operation paralleled the degree of neuromuscular block and were reduced after fentanyl bolus, isoflurane or morphine. Loss of MEPs or persistent amplitude decrements were associated with neurological complications in one patient and severe blood loss in another two patients. MEPs were obtainable in 61% of patients during isoflurane anaesthesia and became inconsistent for end-tidal concentrations >0.87+/-0.08%. Amplitudes were smaller (85 microV) and baseline variability higher (coefficient of variation 29%) than in the propofol group. The decrease in the number of recordings was greater for isoflurane than propofol when the number of pulses/train decreased from 4 to 2. CONCLUSIONS: Muscle MEPs to MP-TES are a safe, sensitive and reliable method for monitoring motor pathways during propofol/nitrous oxide and fentanyl or remifentanil anaesthesia. MEPs are also obtainable in the majority of patients during isoflurane/nitrous oxide anaesthesia, but quantitative monitoring is not always possible with this regimen.

Adolescent↗
PubMed2001

Comparison of the phenotype of NK1R-/- mice with pharmacological blockade of the substance P (NK1 ) receptor in assays for antidepressant and anxiolytic drugs.

The phenotype of NK1R-/- mice was compared with that of acute pharmacological blockade of the tachykinin NK1 receptor on sensorimotor function and in assays relevant to depressive illness and anxiety. The dose range for L-760735 and GR205171 that was associated with functional blockade of central NK1 receptors in the target species was established by antagonism of the behavioural effects of intracerebroventricular NK1 agonist challenge in gerbils, mice and rats. The caudal grooming and scratching response to GR73632 was absent in NK1R-/- mice, confirming that the receptor had been genetically ablated. There was no evidence of sedation or motor impairment in NK1R-/- mice or following administration of L-760735 to gerbils, even at doses in excess of those required for central NK1 receptor occupancy. In the resident-intruder and forced swim test, the behaviour of NK1R-/- mice, or animals treated acutely with L-760735 or GR205171, resembled that seen with the clinically used antidepressant drug fluoxetine. However, the effects of GR205171 were not clearly enantioselective in mice. In contrast, although NK1R-/- mice also exhibited an increase in the duration of struggle behaviour in the tail suspension test, this was not observed following pharmacological blockade with L-760735 in gerbils or GR205171 in mice, suggesting that this may reflect a developmental alteration in the knockout mouse. There was no effect of NK1 receptor blockade with L-760735 in guinea-pigs or GR205171 in rats, or deletion of the NK1 receptor in mice, on behaviour in the elevated plus-maze test for anxiolytic activity. These findings extend previous observations on the phenotype of the NK1R-/- mouse and establish a broadly similar profile following acute pharmacological blockade of the receptor. These studies also serve to underscore the limitations of currently available antagonists that are suitable for use in rat and mouse behavioural assays.

Animals↗
PubMed2001

Surgical treatment for rheumatoid neck arthritis bilateral occipitospinal fusion with plate fixation.

UNLABELLED: The results of surgical treatment of 12 patients with rheumatoid cervical spine arthritis were reviewed. The Ranawat classification was as follows: 5 with Ranawat IIIB, 1 Ranawat IIIA and 6 Ranawat II. Decompression and fusion using autogenous iliac bone graft and double occipitospinal plate fixation was carried out on 11 of these patients; the remaining patient underwent upper cervical spine fusion using screw and wire fixation. The main indication for surgery was neurological deterioration. In three cases previous surgery had been carried out on the cervical spine. The results were assessed at a mean follow-up of 26.1 months. According to Frankel's grading the neurological recovery in patients with neurological compression was one grade. There was clinical and radiological evidence of fusion in all these patients. The following complications required further surgery: acute postoperative epidural hematoma (one patient) screw loosening (one patient) CONCLUSION: Fusion of the occiput and lateral mass of the involved cervical spine using a plate on each side provides a relatively stable fixation in patients with rheumatoid arthritis of the cervical spine. Laminectomy and adequate decompression of the neural elements can be carried out without compromising spinal stability. There is a relatively high complication rate associated with surgery for rheumatoid neck and the patient needs to be informed.

Adult↗
PubMed2000

Surface electrode somatosensory-evoked potentials in spinal surgery: implications for indications and practice.

STUDY DESIGN: A retrospective study of 442 major spinal operations with spinal cord monitoring performed in a University Hospital between 1982 and 1992 was performed. OBJECTIVES: To assess the reliability of the authors' method for monitoring by somatosensory-evoked potential recording, to determine criteria for intraoperative corrective action, and to redefine the need for the wake-up test. SUMMARY OF BACKGROUND DATA: The routine use of somatosensory-evoked potential monitoring in spinal surgery remains controversial. In Nottingham, the authors have used a method of recording from either scalp or high cervical electrodes. METHODS: The recordings and outcomes of all monitored spinal operations between the years 1982 and 1992 were reviewed. RESULTS: In 442 procedures, 23 technical failures (no reliable monitoring) occurred. Most technical failures were in patients with severe preoperative neurology, identifiable by somatosensory-evoked potential recording before operation. In the remaining 419 procedures, a significant intraoperative change in response occurred in 70 procedures (16.7%). Using the definitions of the American EEG Society, the authors identified 10 true-positives and 60 false-positives. There were no false-negatives. A wake-up test was performed if an amplitude drop greater than 50% from baseline value persisted after attempts to correct any possible identifiable intraoperative cause. This occurred in only 21 patients (5%). In the true-positive group, somatosensory-evoked potential recordings remained persistently abnormal despite an apparently normal subsequent wake-up test. The sensitivity of the method according to current definitions was 100% and the specificity 85.33%. CONCLUSIONS: Modified guidelines are needed for routine intraoperative use of somatosensory-evoked potential monitoring in spinal surgery. Such guidelines should avoid the term "false-positive" as currently defined and concentrate on the causative analysis of abnormal responses that warn of critical spinal cord dysfunction before that becomes irreversible and allow for appropriate action. Information from this monitoring method alerted the surgeon to the possible need for corrective action in an additional 9.78% of the reported patients, who traditionally would have been regarded as false-positives. A wake-up test still is indicated in patients with persistent suppression of their somatosensory-evoked potential despite correction of any identifiable cause and in cases of technical failure. The current method proved flexible, versatile, and reliable for future use.

Adolescent↗
PubMed2000

Hybrid computer-guided and minimally open surgery: anterior lumbar interbody fusion and translaminar screw fixation.

Less invasiveness is the way forward for spinal surgery. Minimal disruption of tissue, preservation of muscle function, and restoration of normal spinal alignment are still the goals of most surgical procedures. An anterior lumbar fusion technique using a less invasive procedure with the addition of translaminar screws is described. The autograft is harvested from the vertebral body, thus avoiding the morbidity associated with an iliac crest bone graft. The operative steps for the procedure are described.

Bone Screws↗
PubMed2000

Anterior thoracoscopic surgery followed by posterior instrumentation and fusion in spinal deformity.

Many authors believe thoracoscopic surgery is associated with a lower level of morbidity compared to thoracotomy, for anterior release or growth arrest in spinal deformity. Others believe that anterior release achieved thoracoscopically is not as effective as that achieved with the open procedure. We evaluated the clinical results, radiological correction and morbidity following anterior thoracoscopic surgery followed by posterior instrumentation and fusion, to see whether there is any evidence for either of these beliefs. Twenty-nine patients undergoing thoracoscopic anterior release or growth arrest followed by posterior fusion and instrumentation were evaluated from a clinical and radiological viewpoint. The mean follow-up was 2 years (range 1-4 years). The average age was 16 years (range 5-26 years). The following diagnoses were present: idiopathic scoliosis (n = 17), neuromuscular scoliosis (n = 2), congenital scoliosis (n = 1), thoracic hyperkyphosis (n = 9). All patients were satisfied with cosmesis following surgery. Twenty scoliosis patients had a mean preoperative Cobb angle of 65.1 degrees (range 42 degrees-94 degrees) for the major curve, with an average flexibility of 34.5% (42.7 degrees). Post operative correction to 31.5 degrees (50.9%) and 34.4 degrees (47.1%) at maximal follow-up was noted. For nine patients with thoracic hyperkyphosis, the Cobb angle averaged 81 degrees (range 65 degrees-96 degrees), with hyperextension films showing an average correction to 65 degrees. Postoperative correction to an average of 58.6 degrees was maintained at 59.5 degrees at maximal follow-up. The average number of released levels was 5.1 (range 3-7) and the average duration of the thoracoscopic procedure was 188 min (range 120-280 min). There was a decrease in this length of time as the series progressed. No neurologic or vascular complications occurred. Postoperative complications included four recurrent pneumothoraces, one surgical emphysema, and one respiratory infection. Thoracoscopic anterior surgery appears a safe and effective technique for the treatment of paediatric and adolescent spinal deformity. A randomised controlled trial, comparing open with thoracoscopic methods, is required.

Adolescent↗
PubMed2000

Analgesic and toxic effects of ABT-594 resemble epibatidine and nicotine in rats.

The present study directly compared the antinociceptive and toxic effects of the neuronal nicotinic receptor agonist ABT-594 ((R)-5-(2-azetidinylmethoxy)-2-chloropyridine) with (-)-nicotine and (+)-epibatidine. Like (-)-nicotine (0.8 and 1.6 mg/kg s.c.) and (+)-epibatidine (0.005 and 0.01 mg/kg s.c.), ABT-594 (0.05 and 0.1 mg/kg s.c.) increased response latencies in the hot-plate test in rats, indicating that it has antinociceptive activity. In contrast to (-)-nicotine and (+)-epibatidine, ABT-594 did not cause rotarod impairment at antinociceptive doses but did cause hypothermia and life-threatening adverse effects including seizures. ABT-594 (0.01 and 0.1 mg/kg i.v.) also produced a dose-dependent increase in blood pressure resembling that observed with (-)-nicotine (0.03, 0.1 and 0. 03 mg/kg i.v.) and (+)-epibatidine (0.001 and 0.003 mg/kg i.v.). Both the antinociceptive and toxic effects (convulsions and hypertension) were abolished by pretreatment with the brain penetrant neuronal nAChR antagonist mecamylamine (1 mg/kg s.c.; i.v. for cardiovascular studies), demonstrating that these actions of ABT-594 were mediated via activation of neuronal nicotinic receptors. Continuous infusion of ABT-594 (0.2 mg/kg per day s.c.) to rats for 7 days followed by challenge with mecamylamine (1 mg/kg i.p.) induced a nicotine-like abstinence syndrome suggesting that ABT-594 has nicotine-like dependence liability. These findings indicate that the acute safety profile of ABT-594 is not significantly improved over other nicotinic analgesics.

Analgesics, Non-Narcotic↗
PubMed2000

Spinal instrumentation for primary pyogenic infection report of 31 patients.

The role of spinal instrumentation in the presence of infection is still controversial. Radical debridements of infected vertebrae and disc material and bone grafting usually leaves the spine unstable without some surgical stabilisation. We reviewed 31 cases of primary pyogenic spinal infection treated by radical debridement, bone grafting and posterior (30) or anterior (1) spinal instrumentation. The indication for surgery was the failure of conservative treatment (8), progressive neurological deficit (19) or the lack of diagnosis (3). The clinical, laboratory and radiological parameters were assessed pre and postoperatively. The mean period of follow-up was 3.8 years (1-12 years). The neurological deficit was progressive in 19 patients, following surgery all these patients were improved. The neurological deficit was established in one patient; following surgery, his neurological deficit did not improve. The infection was eradicated in all our patients. The following complications were encountered: (1) three patients developed deep wound infection, which responded to repeated debridement; (2) one death resulted from nosocomial septicaemia, (3) reoperation was carried out on one patient for implant failure and on another for a dislodged anterior bone graft. We conclude that spinal instrumentation may be indicated when after radical debridement of infected vertebrae and disc material and bone grafting the stability of the spine is still compromised. According to the location of the infection and the availability of suitable implants, anterior or posterior instrumentation may be necessary. With appropriate antimicrobial agents, the outcome has been satisfactory in our patients.

Adolescent↗
PubMed1999

Luque trolley and convex epiphysiodesis in the management of infantile and juvenile idiopathic scoliosis.

STUDY DESIGN: Retrospective analysis of 5-year follow-up data from patients instrumented with Luque trolley with or without convex epiphysiodesis for management of progressive infantile and juvenile idiopathic scoliosis. OBJECTIVE: To assess results, establish predictors of outcome, and suggest more effective surgical interventions. SUMMARY OF BACKGROUND DATA: Initial results have been reported. There are no long-term follow-up studies. METHODS: Luque trolley instrumentation was used in eight patients with idiopathic scoliosis between 1983 and 1984. Luque trolley with convex epiphysiodesis was used in 18 patients between 1984 and 1990. RESULTS: Changes in Cobb angle from 8-week to 5-year follow-up are as follows. For Luque trolley alone, Cobb angle worsened for all patients. For progressive infantile scoliosis managed with Luque trolley and convex epiphysiodesis, Cobb angle worsened in seven, remained unchanged in four, and improved in two patients. Mean age at operation was 3.1 years (range, 1.5-7.4 years), and instrumented spinal growth was 32% of expected growth. Preoperation Cobb angle was 65 degrees (range, 40-95 degrees). Cobb angle at 5-year follow-up was 32 degrees (range, 0-86 degrees), which is predicted by preoperation apical concave rib-spinal angle (P = 0.002) and upper end vertebral tilt (P = 0.04). For juvenile idiopathic scoliosis managed with Luque trolley and convex epiphysiodesis, Cobb angle worsened in three patients and improved in one. CONCLUSIONS: Luque trolley instrumentation alone does not prevent curve progression. Additional convex epiphysiodesis results in curve resolution in some patients, which suggests a growth effect. Both spine and rib factors predict Cobb angle at 5-year follow-up.

Braces↗
PubMed1999

Onset and progression of motor deficits in motor neuron degeneration (mnd) mice are unaltered by the glycine/NMDA receptor antagonist L-701,324 or the MAO-B inhibitor R(-)-deprenyl.

NMDA-mediated neurotoxicity and oxidative stress have been implicated in the etiology of a number of degenerative diseases including motor neuron disease. The present study examined the effect of chronic administration of the glycine/NMDA receptor antagonist L-701,324 and the monoamine oxidase B inhibitor (r)-deprenyl on the onset and rate of progression of neurological impairment in the motor neuron degeneration (mnd) mouse, a murine model of neurodegeneration. Neurological assessment of mnd mice revealed an onset of motor deficits at 6 months of age as observed by the loss of hindlimb reflex extension. By 7 months, balance was also markedly impaired as measured by deficits in rotarod performance and ability to remain on balancing beams. At 8 months of age mnd mice exhibited gross abnormalities in walking pattern; animals were unable to flex their hindlimbs and tended to walk in small labored movements. Daily administration of L-701,324 (10 mg/kg p.o.) or r(-)-deprenyl (1 mg/kg p.o.) to mnd mice from 4 to 8 months of age failed to delay the onset of symptoms or slow the rate of deterioration of motor performance. These findings suggest that excessive activation of NMDA receptors may not be involved in the pathological process leading to motor neuron dysfunction in mnd mice and do not suggest a protective effect of deprenyl on motor neurons in these mice.

Animals↗
PubMed1999

Selective NMDA NR2B antagonists induce antinociception without motor dysfunction: correlation with restricted localisation of NR2B subunit in dorsal horn.

The present study investigated the regional distribution of the N-methyl-D-aspartate (NMDA) receptor containing the NR2B subunit protein in rat lumbar spinal cord and examined whether selective NR2B antagonists would exhibit antinociception with reduced side-effect liability than subtype non-selective NMDA antagonists and anticonvulsants. Immunocytochemical studies showed the NR2B subunit had a restricted distribution, with moderate labelling of fibres in laminas I and II of the dorsal horn suggesting a presynaptic location on primary afferent fibers and possible involvement in pain transmission. In the in vivo studies, the NMDA/glycine antagonists (MK-801, 0.02-1 mg/kg i.p., L-687,414 10-300 mg/kg i.p., and L-701,324 1-10 mg/kg i.p.) and the anticonvulsant, gabapentin (10-500 mg/kg p.o.), induced rotarod deficits at antinociceptive doses. In contrast, the selective NR2B antagonists, (+/-)-CP-101,606 (1-100 mg/kg p.o.) and (+/-)-Ro 25-6981 (3-100 mg/kg i.p.) showed a significant dose window. (+/-)-CP-101,606 caused no motor impairment or stimulation in rats at doses up to 100 mg/kg p.o., which is far in excess of those inhibiting allodynia in neuropathic rats (ID50 4.1 mg/kg, p.o.). (+/-)-Ro 25-6981 also showed a significant separation (ID50 allodynia 3.8 mg/kg, i.p.), however, some disruption of rotarod performance was observed at 100 mg/kg. The anticonvulsant lamotrigine (3-500 mg/kg p.o.) also showed a good dose window. These findings demonstrate that NR2B antagonists may have clinical utility for the treatment of neuropathic and other pain conditions in man with a reduced side-effect profile than existing NMDA antagonists.

Acetates↗