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Biomedical subjects

B A Bell

Publications and source records attributed to B A Bell.

At least 19 recordsLinked to original sources

Magnetic resonance neurography.

We have made cross-sectional image "neurograms" in which peripheral nerve has a greater signal intensity than that of other tissue. Neurographic images of the rabbit forelimb were obtained using a spin-echo magnetic resonance imaging (MRI) technique that combines fat suppression and diffusion weighting. After fat suppression the nerve shows up in relative isolation and is brighter than the surrounding tissue due to its longer T2 relaxation time of approximately 50 ms compared to approximately 27 ms for muscle. The addition of pulsed gradients for diffusion weighting of the MR signal further enhances the intensity of the nerve signal relative to that of surrounding muscle tissue. The greater diffusional anisotropy of nerve tissue (D parallel/D perpendicular = 3.1) compared to that of muscle (D parallel/D perpendicular = 1.9) allows further enhancement of the nerve by a subtraction of two diffusion-weighted images, one with the gradients oriented parallel and one with the gradients oriented perpendicular to the nerve orientation. We show that by manipulation of the MRI parameters, either echo time or pulsed gradient strength, the nerves can be made to show up as the most intense feature. This verifies the feasibility of generating three-dimensional "neurographic" images, analogous to angiograms, but which demonstrate the peripheral nerve tracts in apparent isolation.

Adipose Tissue

Palmitoyl-DL-carnitine has calcium-dependent effects on cultured neurones from rat dorsal root ganglia.

1. The effects of palmitoyl-DL-carnitine (0.01 to 1 mM) on whole cell voltage-activated calcium channel currents carried by calcium or barium and Ca(2+)-activated chloride currents were studied in cultured neurones from rat dorsal root ganglia. 2. Palmitoyl-DL-carnitine applied to the extracellular environment or intracellularly via the patch solution reduced Ca2+ currents activated over a wide voltage range from a holding potential of -90 mV. Inhibition of high voltage activated Ca2+ channel currents was dependent on intracellular Ca2+ buffering and was reduced by increasing the EGTA concentration from 2 to 10 mM in the patch solution. Barium currents were significantly less sensitive to palmitoyl-DL-carnitine than Ca2+ currents. 3. The amplitude of Ca(2+)-activated Cl- tail currents was reduced by palmitoyl-DL-carnitine. However, the duration of these Cl- currents was greatly prolonged by palmitoyl-DL-carnitine, suggesting slower removal of free Ca2+ from the cytoplasm following Ca2+ entry through voltage-activated channels. 4. Palmitoyl-DL-carnitine evoked Ca(2+)-dependent inward currents which could be promoted by activation of the residual voltage-activated Ca2+ currents and attenuated by intracellular application of EGTA. 5. We conclude that palmitoyl-DL-carnitine reduced the efficiency of intracellular Ca2+ handling in cultured dorsal root ganglion neurones and resulted in enhancement of Ca(2+)-dependent events including inactivation of voltage-activated Ca2+ currents. The activation of inward currents by palmitolyl-DL-carnitine may involve Ca(2+)-induced Ca2+ release from intracellular stores, or direct interaction of palmitoyl-DL-carnitine with Ca2+ stores.

Animals

Is peroperative smear cytology necessary for CT-guided stereotaxic biopsy?

Neuropathology is a relatively scarce resource with uneven geographical distribution, and some surgeons rely on macroscopic appearances of tissue and await later paraffin section histology for the final diagnosis. The effect of the introduction of a peroperative cytology service has been assessed in a 5-year series of CT-directed stereotaxic biopsies of intracranial mass lesions using a low cost adapted pre-CT stereotaxic frame. The technique has been mastered by 28 different surgeons with varying degrees of neurosurgical expertise and 259 procedures have been performed in 245 patients. Benign lesions were detected in 24 (9.8%) patients, confirming the importance of making a histological diagnosis prior to initiating treatment. Permanent morbidity was 6.5% and mortality 3.3% and morbidity was balanced by an improvement in 19.6% of the patients following the procedure. For the first 142 patients no peroperative histological diagnosis was available and a diagnostic rate of 86.6% was achieved. For the last 103 patients the availability of peroperative smears improved the diagnostic rate to 94.2% and reduced the number of second biopsies needed for diagnosis from seven to zero. Our series demonstrates the need for peroperative cytology in CT stereotaxic biopsies, and confirms that a complete neuropathology service is a prerequisite for neurosurgical patient care.

Adolescent

Binaural cochlear implants.

With the success of monaural cochlear implantation, patients frequently ask about having a second implant. We have performed binaural cochlear implants in 12 adult patients. Desire not to disrupt a functioning implant was the primary consideration in implanting the contralateral ear. Seven patients received a second 3M/House single-channel implant to upgrade to a magnetic external receiver. Four patients with a 3M/House device in one ear elected to place a Nucleus multichannel implant in the opposite ear. One patient with a poorly functioning Nucleus device elected to have a second Nucleus device. Four patients with a Nucleus and a 3M/House implant, one with binaural 3M/House implants, and one with binaural Nucleus implants were tested for auditory discrimination in order to quantify monaural versus binaural differences. The functional benefit of the second implant was mixed, but all patients showed some degree of objective improvement on one or more tests. Five of the six are regular users of both devices; the patient with binaural Nucleus implants wears only one. Despite the differing processing schemes, patients with a Nucleus device in one ear and a 3M/House device in the other ear are able to combine the two signals to advantage. We feel that cochlear implantation in the contralateral ear is an acceptable option in selected patients desiring an upgraded implant without placing a functioning implant at risk.

Aged

Phase II study of 13-cis-retinoic acid in pediatric patients with acute nonlymphocytic leukemia--a Pediatric Oncology Group study.

Forty-one patients with refractory acute non-lymphocytic leukemia (ANLL) in relapse were treated with 13-cis-retinoic acid (cRA) as salvage therapy. The cRA was given as a single oral dose of 100 mg/m2/day for 4 weeks. One patient achieved a complete remission and two patients achieved a partial remission with reduction of the bone marrow blast count from 40 to 20% after the first course. We recommend further study of cRA in combination with other agents in the treatment of ANLL in children.

Adolescent

Improved access to lesions of the central skull base by mobilization of the zygoma: experience with 54 cases.

Improved access to lesions at the medial end of the sphenoid wing or in the interpeduncular cistern after mobilization of the zygoma has been a subject of growing interest in recent years. This study describes the operative technique we have adopted and records our experience with 55 operations in 54 patients who underwent the procedure in the past 3 years. Seven patients had vascular lesions, 44 had tumors, and 3 had miscellaneous lesions. The majority of the tumors were medial meningiomas, and particular note is made of those arising from the cavernous sinus with respect to their resectability. Sixteen of these tumors were encountered, and total excision was possible in 11 cases. Access to the infratemporal fossa is facilitated, and in 2 cases we were able to excise completely trigeminal neuromas that had extended there. The extra maneuver adds little to the overall operating time, and complications relating to it are uncommon, mild in degree, and usually self-limiting. We conclude that the operation is extremely valuable in appropriate circumstances.

Adolescent

Postoperative radiotherapy in the management of spinal cord ependymoma.

Fifty-eight patients with histologically verified spinal cord ependymomas were treated at the Royal Marsden Hospital and Atkinson Morley's Hospital between 1950 and 1987. The median age in this series was 40 years (range 1 to 79 years) and the male:female ratio was 1.8:1. Ten patients had tumors in the cervical cord and 10 in the thoracic cord; 14 tumors involved the conus medullaris and 24 the cauda equina. Forty ependymomas were grade I and 13 were grades II to IV (in five patients there was insufficient material for grading). Eleven patients underwent biopsy only, 33 had partial or subtotal resection, and 14 had complete resection. Forty-three patients received postoperative radiotherapy. The median follow-up period was 70 months (range 3 to 408 months). Cause-specific survival rates were 74% and 68% at 5 and 10 years, respectively. On univariate analysis, age, histological grade, postoperative neurological function, and era of treatment were significant prognostic factors for survival. The histological grade was the only significant independent prognostic factor. The relative risk of death from ependymoma was 9.0 for patients with tumor grades II to IV compared to grade I (p less than 0.005, 95% confidence interval 2.7 to 30). The survival rates of patients following complete excision were significantly better compared to those after incomplete surgery (p less than 0.025). The majority of completely resected neoplasms were low-grade cauda equina tumors. Despite incomplete surgery, 5- and 10-year progression-free survival rates following radical radiotherapy were both 59%, and cause-specific survival rates were 69% at 5 years and 62% at 10 years. This suggests that radiotherapy may achieve long-term tumor control in over half of those patients with residual spinal ependymoma.

Adolescent

Effect of calcitonin-gene-related peptide on postoperative neurological deficits after subarachnoid haemorrhage.

An infusion of calcitonin-gene-related peptide (CGRP) at progressively increased concentrations was given to 15 patients with neurological deficits after intracranial aneurysm surgery for subarachnoid haemorrhage. In 9 of the patients the deficits, quantified by a modified Glasgow coma scale, improved with no adverse effects; after a placebo infusion only 2 of the 15 patients showed improvement. If CGRP can reverse cerebral ischaemia after early intracranial aneurysm surgery, its use may improve the safety of such early surgery, remove the need for late surgery with its increased risk of death from rebleeding, and reduce overall morbidity and mortality of aneurysmal subarachnoid haemorrhage.

Adult

Craniocervical stabilization using Luque/Hartshill rectangles.

Untreated craniocervical instability is associated with a high morbidity and a significant mortality. Existing methods using bone grafts, interlaminar wires, or acrylic eventually produce stability but require prolonged periods of immobility and have a high failure rate. The ideal method of fixation should provide for permanent correction of deformity and relief of symptoms, with immediate stabilization, at a single procedure. Posterior fixation of the occiput to a stable part of the cervical spine with a molded metal rectangle held in place by interlaminar wires was used to accomplish this. We report 20 patients treated consecutively who have undergone craniocervical fusion by this method using Luque/Hartshill rectangles. Fourteen patients had preexisting atlantoaxial instability and 6 had cord compression, but would become unstable after decompression. All operations were performed under general anesthesia; 9 patients (40%) were awake for intubation/positioning, and 7 patients had a simultaneous decompression. Sixteen patients made an uncomplicated recovery and became mobile 3 days postoperatively. Symptomatic and neurological improvement occurred in 70% of all patients. Neurological complications occurred in 4 patients (20%), reflecting the serious nature of the condition; 2 patients (10%) showed no change. Scrutiny of their presentations and operations failed to identify avoidable risk factors, except faulty wiring techniques. In all patients, permanent stabilization was achieved immediately, facilitating early mobilization with a real chance of improvement, which indicates that the method merits wider application.

Adolescent

A scale for neurosurgical audit.

A neurosurgical audit scale has been devised to provide a measure of disability and outcome. The audit scale was tested for observer variation and sensitivity against the Karnofsky scale, the Rosser disability scale and the Rosser distress scale. The highest ratio of observer concurrence compared with chance was noted for the neurosurgical audit scale, and the lowest ratio for the Rosser distress score. Sensitivity was almost identical for each of the scales. The neurosurgical audit scale lends itself to audit based on a computer database for which the input is the discharge summary. This achieves audit without additional work for either medical or secretarial staff.

Disability Evaluation

Maintenance of normal platelet mass in anemic Belgrade rats and their response to iron.

The Belgrade (b/b) rat has severe hypochromic, microcytic anemia accompanied by mild thrombocytopenia and a 49% reduction in megakaryocytes (MKs). The platelet counts are decreased only 34%, but relative platelet size measured by two independent methods averages 50% greater than controls. Thus, the platelet mass of the b/b rat is within the normal range. The marrow MK progenitors (MK colony-forming units, CFU-MK) respond linearly to increased colony-stimulating activity in vitro, but they are reduced 68% and form smaller colonies than normal. Flow cytometric analysis of MK ploidy indicates that significantly more MKs are distributed into the low and high ploidy classes compared with the normal, and the mean ploidy is similar. The b/b rat maintains effective thrombocytopoiesis in spite of a severe reduction in MK progenitors, primarily by an increased rate of maturation of the endomitotic compartment. Iron treatment partially arrests the b/b anemia and is associated with a significant increase in CFU-MK, a normalized MK ploidy distribution, and a significant decrease in platelet size. The favorable response to iron therapy suggests that the megakaryocytopenia is secondary to the severe anemia and results from stem cell commitment to the erythroid lineage.

Anemia

A low cost system for performing CT stereotaxic brain biopsy.

The cost of commercially available CT-compatible frames for stereotaxic brain biopsy has limited their availability in the U.K. Our adaptation to a pre-CT stereotaxic frame that had been in use at Atkinson Morley's Hospital for 12 years, and the availability of a GE 9800 CT scanner has allowed us to carry out accurate CT-directed stereotaxic biopsy at minimal cost. The system has the additional advantage of speed and ease of use in inexperienced neurosurgical hands. Biopsies in 100 patients have been performed by 12 different surgeons (80% by registrars) who mastered the technique without difficulty. The rates of permanent morbidity (4%) and mortality (2%) are low, the two mortalities occurring in patients with high grade astrocytomas. They compare very favourably with rates for freehand burr-hole biopsy, and our overall diagnostic success rate of 83% for the initial biopsies, rising to 90% as a result of re-biopsy in 10 of the patients, is similar to that achieved with much more costly commercial systems. Benign lesions were found in 7% of patients who would otherwise have been assumed to have malignant tumours, and this finding emphasises the value of achieving a histological diagnosis in every lesion of the brain.

Biopsy

Measurement of changes in brain water in man by magnetic resonance imaging.

John Hunter was undoubtedly aware of the water content of normal brain tissue, and described cerebral oedema. The advent of nuclear magnetic resonance (NMR) shed new light on brain water, and the derivation of spatial information and hence images from NMR signals, has permitted studies of regional brain water in man in vivo. The initial study described here tested whether NMR longitudinal relaxation time (T1) correlates with brain water content in the cerebral cortex and white matter in man, and significant relationships have been demonstrated in cortex (r = 0.65, P less than 0.002) and white matter (r = 0.94, P less than 0.0001), the latter having narrow 95% confidence limits. The residual variance allows the prediction of water content from the T1 of white matter, measured from the image of a single patient, with an accuracy of +/- 4% of total tissue water with 95% confidence. In the further study described, the effects of dexamethasone and an infusion of 20% mannitol on brain water content has been assessed in patients with intrinsic cerebral tumours. Dexamethasone had no significant effect on the T1 of normal brain, oedematous peritumoural white matter, or tumour tissue. It must be concluded that the water content of these tissues is not changed by dexamethasone and that the clinical improvement seen in patients with cerebral tumours immediately after dexamethasone has to be explained by some mechanism other than a reduction in cerebral oedema. Mannitol did reduce the T1 of oedematous peritumoural white matter, and the T1 of tumour tissue, but did not change the T1 of normal brain significantly. Thirty minutes after starting the mannitol infusion,water content of the oedematous white matter had been reduced by 1.4%. John Hunter studied the structure and social habits of the honeybee extensively for almost 40 years before he eventually published his findings. Steroids and osmotic agents have been used to treat brain oedema for over 40 years, but their precise mechanisms of action still require further elucidation. Magnetic resonance will hopefully continue to shed further light on this clinically important area.

Adult