[New patients' rights can create unrealistic expectations. Interview by Bjørn Arild Ostby].
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Biomedical subjects
Publications and source records attributed to P Roland.
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Nimodipine, an antagonist of the L-type calcium ion channel, was labelled with 11C for in vivo positron emission tomography studies of dihydropyridine binding in the human brain. The synthesis was based on esterification of the corresponding acid (W2100) using [2-11C]isopropyl iodide as the labelling precursor. The effects of different bases, solvent mixtures and reaction temperatures on radiochemical yields were investigated. The synthesis including purification by semi-preparative reversed-phase HPLC, required 60-65 min. Conversion of [2-11C]isopropyl iodide to [isopropyl-11C] nimodipine was of the order of 60-80%. The radiochemical yield (isolated) was 20-25%, based on [11C]carbon dioxide. The specific activity of the isolated product varied from 4-40 GBq/mumol (end-of-synthesis).
Sodium thiocyanate (NaSCN) was labelled with carbon-11 for in vivo studies of anion kinetics using positron emission tomography (PET). The synthesis was complete in 35 min from end of bombardment using [11C]ammonium cyanide as the labelled precursor. [11C]NaSCN was produced by the reaction of [11C]sodium cyanide with elemental sulfur and subsequently separated by semi-preparative high performance liquid chromatography (HPLC). Radiochemical yields (isolated) were of the order of 25%. The specific activity was 18 GBq/mmol and the radiochemical purity better than 99%. A PET study performed in a healthy volunteer showed distribution of [11C]SCN- to areas corresponding to cortical fluid spaces known to be accessible to inorganic ions such as Cl-. An accumulation of the tracer was observed during the 70 min investigation, indicating at least three compartments of distribution.
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Ten patients with partial epilepsy and five healthy controls had positron emission tomography (PET) of the brain after intravenous administration of the 11C-labelled benzodiazepine (BZ) receptor ligand 'Ro-15 1788'. In all ten patients BZ receptor binding was significantly lower in the epileptic focus than in the contralateral homotopic reference region and the remaining neocortex. No asymmetries in BZ receptor binding were observed between homotopic reference regions in the controls or the non-epileptic regions of patients. These results demonstrate the potential of the BZ receptor as a biochemical marker for display of epileptic foci by PET, and also strengthen the hypothesis that inhibitory mechanisms are disturbed in the epileptic focus.
Human alpha-calcitonin gene-related peptide (CGRP) is a substance immunohistochemically present in a number of organ systems; however, the biologic significance of this peptide is uncertain. The present study was undertaken to investigate the effects of CGRP in the feline mesenteric vascular bed under conditions of controlled blood flow. Bolus injections of CGRP decreased mesenteric perfusion pressure in a dose-related fashion. When compared with nitroglycerin, CGRP possesses markedly greater vasodilator activity in the intestinal vascular bed of the cat. Because circulating levels of CGRP have been identified, the present data suggest CGRP may play a role in the regulation of systemic vasomotor tone and regional hemodynamics, as well as involve altered calcium metabolism seen with other calcium-regulating hormones in hypertensive states.
Fluoromethane, previously labelled with 18F and used as a tracer in the measurement of regional cerebral blood flow, was 11C-labelled by the reaction of 11C-methyl iodide with tetraethylammonium fluoride. Sufficient quantities of radiotracer were prepared with a minimum amount of handling from 15 min target irradiations in the 14N(p, alpha)11C reaction. Total synthesis time was 25 min from end-of-bombardment, allowing serial blood flow measurements 30 min apart. The use of 11C-fluoromethane as a cerebral blood flow tracer in positron emission tomography is discussed.
Ten skull-base neuromas treated at the Otology Group P.C. are presented. Each case is reported in detail. The method by which preoperative diagnosis was made is reviewed. Specific attention is paid to distinguishing these tumors from chemodectomas. Presenting signs and symptoms are enumerated. Operative--especially postoperative--management is discussed in detail.
The regional uptake of 99Tcm-labelled HMPAO has been measured with single photon emission computed tomography (SPECT). The potential value of 99Tcm-HMPAO as a flow tracer was evaluated. The uptake of 99Tcm-HMPAO as a function of time indicated that the tracer was trapped in the brain. The uptake images were compared with results from quantitative regional cerebral blood flow (rCBF) measurements using positron emission tomography (PET) and with 11C-fluoromethane used as a tracer. There was a strong correlation between the uptake of 99Tcm-HMPAO and rCBF. The conclusion was that the uptake of 99Tcm-HMPAO was dependent on rCBF.
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A 13-year-old boy undergoing tympanoplasty lasting 3 1/2 hours developed serious airway obstruction at the end of surgery leading to permanent brain damage. It appeared that the no. 7 Portex "blue line" endotracheal tube had collapsed under the cuff. This was concluded because deflation of the cuff had promptly relieved the obstruction of the airway. Further support for this conclusion was the finding that shortly after extubation the inflation of 8 ml air caused the tube to collapse. Collapse of these tubes cannot normally be produced unless they have been made to collapse shortly before. Investigation of such tubes in vitro at 37 degrees C showed that overinflation of the cuff caused a symmetrical collapse of the tube wall along the x-ray opaque blue line. The collapse occurred with cuff pressures varying from 310 mmHg up to 460 mmHg for tubes from different batches. During anaesthesia with 66% nitrous oxide, this gas together with carbon dioxide were found to diffuse into the cuff at steady rates of 3.69 vol % and 0.36 vol % per hour, respectively. Corresponding increases in intracuff volumes were found. It is advised that disposable tubes should be carefully inspected before use and that endotracheal cuffs should be deflated periodically during anaesthesia to avoid excessive rise in cuff pressure.
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Impaired cortical inhibition may be involved in epileptogenic mechanisms. In a positron-emission tomography (PET) study, we demonstrated a reduction of the cortical benzodiazepine (BZD) receptor density in the epileptic foci of patients with partial epileptic seizures. In the present study, we used the same method in 10 patients with primary generalized epilepsy to determine whether an altered BZD receptor binding could also be demonstrated in this patient group. The [11C]-labeled BZD receptor antagonist Ro 15-1788 was used as ligand. Receptor affinities and densities were calculated in various cortical regions and then compared with the values from corresponding "nonepileptic" regions in the previously examined partial epilepsy patients. Focal alterations of the BZD receptor density or affinity were not demonstrated in patients with generalized epilepsy. This patient group had a slight tendency toward lower mean cortical BZD receptor density, however, as compared with corresponding values from 10 patients with partial epilepsy. Our results strongly suggest that a focal alteration of cortical inhibition is not a prominent feature of human generalized epilepsy. The observed tendency toward lower mean cortical BZD receptor density may be a consequence of diffusely impaired cortical inhibition. Further investigations of this issue are therefore indicated.