3H]Ro 19-6327: a reversible ligand and affinity labelling probe for monoamine oxidase-B

This study demonstrated the existence of specific binding sites for [3H]Ro 19-6327 in human platelet membranes. This compound is a novel, time-dependent inhibitor of monoamine oxidase type B (MAO-B) and is structurally closely related to [3H]Ro 16-6491. The density of the sites labelled with high affinity by [3H]Ro 19-6327 was similar to that observed in previous studies with [3H]Ro 16-6491 as ligand. Binding was reversible at 20 degrees C and showed a relatively slow dissociation (t1/2 = 220 min). The dissociation rate was markedly decreased (t1/2 = greater than 24h) at 0 degrees C. MAO-B, but not MAO-A inhibitors, effectively prevented the binding of [3H]Ro 19-6327. Like [3H]Ro 16-6491, [3H]Ro 19-6327 is recognized as a substrate by MAO-B, being eventually deaminated by the enzyme. Since the deaminated aldehyde derivative of Ro 19-6327 did not inhibit MAO-B, a still unidentified reversible adduct, formed at the MAO-B active site, might explain the high potency and selectivity of [3H]Ro 19-6327. Incubation of the radioligand-enzyme complex from platelet and brain membranes with NaBH3CN and acetic acid (to pH 4.5) caused the irreversible incorporation of the radioactivity into a single polypeptide as shown by SDS-PAGE analysis. This polypeptide had a molecular weight identical to that of the MAO-B subunit, i.e. 58,000. The presence of unlabelled MAO-B inhibitors in the incubation mixture prevented the covalent incorporation of [3H]Ro 19-6327. The irreversible MAO-B inhibitor, [3H] pargyline, labelled a protein with a molecular weight identical to the protein labelled by [3H]Ro 19-6327.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thoracic disc herniation in acromegaly

Herniation of a thoracic disc in an acromegalic giant is reported. Degenerative changes in the spine in association with dorsal kyphosis, and the additional strain, resulted in the disc prolapse.     

Efficacy of transdermal clonidine for headache prophylaxis and reduction of narcotic use in migraine patients. A randomized crossover trial

Thirty patients completed a double-blind, randomized crossover study utilizing transdermal clonidine and an identical-appearing placebo. Crossover occurred at 6 weeks, with a total study time of 12 weeks. Subjects were asked to record daily in a special diary (1) the presence or absence of headache, (2) duration of headache, (3) severity of headache, and (4) use of pain medication for headache relief. The severity of the headaches was rated from 1 (very mild) to 5 (very severe). Although the subjects reported a decrease in frequency, duration, and intensity of headaches while using the medicated patch, these differences did not reach statistical significance. Nineteen patients subjectively preferred the medicated patch, while five preferred the placebo (P less than .01). During use of the medicated patch, a significant reduction (P = .039) occurred in use of class II narcotics. Three doses of these substances were used by the patients when treated with clonidine, while 34 doses were taken during placebo use. These findings suggest that clonidine might have a role in reduction of parenteral narcotic use in acute pain syndromes.     

Release of cortical catecholamines by visual stimulation requires activity in thalamocortical afferents of monkey and cat

Catecholamine (CA) release was measured in vivo in the monkey and cat visual cortices electrochemically. Stereate-modified, graphite-paste electrodes were used to monitor changes in norepinephrine and dopamine release. Micromolar changes in CA concentration were obtained by stimulation of the eye with nonspecific (strobe) or specific (oriented bars, radial gratings) stimuli. CA release depended on which eye was illuminated. Electrodes passed tangentially through the striate area recorded release following visual stimulation of one eye or the other in succession, and the shift in eye dominance occurred at about 500 microns intervals. The magnitude of CA release was highly correlated with the ocular dominance of neuronal activity measured with tungsten microelectrodes. Light-stimulated release was not recorded in monkey area V2, V4, or somatosensory area 1, but was recorded in cat V2, suggesting that the presence of LGN afferents is associated with CA release. Results are discussed in terms of the role of geniculate activity and the specific role of CAs in cortical information processing.     

Acute ureteral colic from an obstructing renal aspergilloma

Fungus balls of the renal collecting system are rarely of organisms other than Candida. A case of obstructing aspergilloma associated with acute ureteral colic is presented. The clinical features of this case are characteristic of renal aspergillomas in 10 additional cases described in the literature. Ten of the 11 patients were male. Each of the patients had an underlying disease that predisposed to fungal infection. Although all 11 patients were cured, diagnostic evaluation was often protracted as commoner causes of ureteral obstruction were excluded. Successful therapy required evacuation of the obstructing hyphal mass; open surgical procedures were necessary in five instances. Systemic amphotericin B should be reserved for patients with residual infection following removal of the fungus ball. This report emphasizes the need to consider aspergilloma in the differential diagnosis of acute ureteropelvic obstruction in the appropriate patient population.