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Biomedical subjects

B A Bell

Publications and source records attributed to B A Bell.

At least 55 records · Page 3Linked to original sources

Calcitonin gene-related peptide reduces brain injury in a rat model of focal cerebral ischemia.

BACKGROUND AND PURPOSE: Calcitonin gene-related peptide is an endogenous vasodilating neuropeptide with a dense concentration in the trigeminocerebrovascular system. It is hypothesized that depletion of this peptide contributes to delayed cerebral ischemia after subarachnoid hemorrhage and that an exogenous supply of calcitonin gene-related peptide will augment ischemic cerebral blood flow and reduce neuronal injury. METHODS: In this study we have investigated the effect of an intravenous infusion of calcitonin gene-related peptide (100 ng/kg per minute), started 1 hour before and continued throughout 4 hours of focal cerebral ischemia, on cerebral blood flow and the volume of brain injury in a rat model of middle cerebral artery occlusion. RESULTS: Calcitonin gene-related peptide produces a significant improvement in ischemic cerebral blood flow (32 +/- 2 compared with 13 +/- 2 mL/100 g per minute in the controls; t = 6.92, P < .0001) with a concomitant reduction in the volume of ischemic brain injury (102 +/- 22 compared with 234 +/- 19 mm3; t = 4.47, P < .001). CONCLUSIONS: These findings lend support for the potential use of this peptide in the prophylactic treatment of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

Animals↗

Prolactinomas in men masquerading as invasive skull base tumours.

Four giant prolactin-secreting tumours invading the skull base are described. All of them occurred in men. The presenting features were sufficiently diverse to be clinically misleading. We advocate the estimation of prolactin levels before embarking on complicated skull base surgery in men where doubt remains regarding the diagnosis after clinical and radiological study.

Adolescent↗

Subgaleal haematoma resulting in extradural compression following craniotomy. Report of two cases.

We describe two patients who underwent intracranial aneurysm surgery and developed postoperative subgaleal haematomas which, in the presence of an unfixed bone flap, resulted in significant extradural compression and a marked clinical deterioration. The application of a pressure dressing to tamponade a developing scalp haematoma is unwise unless the bone flap has been rigidly fixed in place.

Adult↗

Magnetic resonance neurography.

Radiological methods exist for generating tissue-specific images of bone, vessels, lymphatics, abdominal viscera, and the central nervous system, but there has been no reliable means to generate a clinical image of a nerve. We present the first "image neurogram" and report a method for producing such images by use of commercial magnetic resonance imaging systems. The image depicts a human nerve in situ in relation with a nerve graft, wherein the nerve is rendered in isolation much like a vessel appears in isolation in a subtraction angiogram.

Adult↗

Stereotactic aspiration of brain abscesses: is this the treatment of choice?

Despite a reduction in the mortality of patients with brain abscess since the introduction of the computed tomography (CT) scanner, controversy persists as to the preferred method of treatment for this condition. Eleven patients were treated by CT guided stereotactic aspiration of pus and appropriate antibiotic therapy. A total of 14 aspirations were performed. Ten abscesses were supratentorial and one was in the posterior fossa. In 9 patients a bacterial cause was identified while in 2 a fungus was identified. A good outcome was achieved in 7 patients but 3 patients died. Another elderly patient remains disabled at home. The deaths occurred in severely systemically ill patients with poor conscious levels on admission. Only one patient has epilepsy, controlled with anticonvulsants while another has not had further seizures since abscess treatment a year ago. Stereotactic aspiration should be considered the treatment of choice in all but the most superficial and largest cerebral abscesses, although the mortality of this condition in the severely ill remains high.

Adolescent↗

An improved linker for single-chain Fv with reduced aggregation and enhanced proteolytic stability.

The effects of linker length on binding affinity and degree of aggregation have been examined in the antifluorescein 4-4-20 and anticarcinoma CC49 single-chain Fvs. Longer linkers in the antifluorescein sFvs have higher affinities for fluorescein and aggregate less. A proteolytically susceptible site between Lys8 and Ser9, in the previously reported 212 linker has been identified. A new linker sequence, 218 (GSTSGSGKPGSGEGSTKG) was designed in which a proline was placed at the C-terminal side of the proteolytic clip site in the 212 linker. The CC49 sFv containing the 218 linker showed reduced aggregation and was found to be more stable to proteolysis in vitro, when compared to the CC49/212 sFv. The CC49 sFv with the longer 218 linker had higher affinity than CC49/212 sFv. An aggregated CC49/212 sFv sample had higher affinity than CC49/218 sFv. The CC49/218 and CC49/212 sFvs had similar blood clearances in mice, while the aggregated CC49/212 sFv remained in circulation significantly longer. In mice bearing LS-174T human colon carcinoma xenografts, the CC49/218 sFv showed higher tumor uptake than the CC49/212 sFv and lower tumor uptake than the aggregated CC49/212 sFv. The higher tumor uptake of the CC49/218 is most likely a result of its higher resistance to proteolysis. The higher affinity and higher tumor uptake of the aggregated CC49/212 sFv are most likely due to the repetitive nature of the TAG-72 antigen and the higher avidity of multivalent aggregates. When the sFvs were radiolabeled with a lutetium-chelate the CC49/218 sFv showed a lower accumulation in the liver and spleen compared to the aggregated CC49/212 sFv.

Amino Acid Sequence↗

Experience with recombinant factor VIIA in an infant hemophiliac with inhibitors to FVIII:C undergoing emergency central line placement. A case report.

An infant boy with severe factor VIII (FVIII) deficiency hemophilia and antibodies against coagulation FVIII is presented. This case is unique from the point of view of the young age of development and recognition of inhibitors to the FVIII and because this patient received recombinant factor VIIa (rFVIIa), prior to a life-saving surgical procedure. Conventional treatment options had been exhausted. The inhibitor was an IgG antibody that had rapidly increased to 100 Bethesda Units (BU). A broviac central line was placed to provide i.v. access for the purpose of treatment. Porcine FVIII had been used but an inhibitor rapidly developed to that product. Using rFVIIa, hemostasis was secured for placement of a second central line and to stop life-threatening mucosal bleeding. rVIIa was an effective treatment alternative for the management of this patient with inhibitors.

Autoantibodies↗

The pathophysiology of infant subdural haematomas.

The widely accepted theories concerning the pathophysiology of infant subdural haematoma (SDH) were formulated in the pre-computed tomographic (CT) scan era. Violent shaking is considered to be a crucial cause of SDH in non-accidentally injured infants. This theory has been re-examined in a clinical and CT scan review, and our findings have been correlated with results of recent head injury research. A retrospective review was conducted of all head injured infants (up to 18 months old) treated at Atkinson Morley's Hospital over a recent 20-year period (n = 100). Twenty-eight infants with a SDH were identified. CT scans were reviewed and each SDH greater than 0.5 cm thick was morphometrically analysed. Seventeen infants were Caucasian, 10 were non-Caucasian and one was of mixed race. A race-dependent pattern of SDH pathophysiology was noted, with non-Caucasian infants with a head injury more likely to have a SDH than Caucasian infants (67 v 21%, p < 0.01). All had a history of, or radiographic and clinical findings most consistent with, an impact injury, and non-Caucasian infants were significantly more likely to have a normal scalp examination despite the impact injury (p < 0.05) and to have developed the SDH after a relatively trivial fall (p < 0.01). They were also more likely to have a large (> 0.5 cm thick) SDH (p < 0.05), and to suffer post-traumatic seizures (p < 0.05). Our findings do not support shaking as the only cause of infant SDH formation and also suggest that non-accidental injury is a less common cause of SDH than it is believed to be.

Child Abuse↗

Midline aneurysms of the vertebrobasilar junction: an effective anterior approach.

There are acknowledged difficulties associated with operations on midline aneurysms at the vertebrobasilar junction. This report describes a series of such aneurysms treated by an anterior approach using a Le Fort maxillotomy to gain access via the clivus to the aneurysm. In each case the aneurysm was dealt with satisfactorily with no long-term morbidity or mortality. Attention is directed to the necessity for a water-tight dural seal postoperatively. We advocate wider use of this technique in appropriate circumstances.

Adult↗

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↗