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)     

Evaluation of the central anticholinergic activity of antidepressants. Comparison of two experimental methods

The anticholinergic effect of atropine, imipramine, clomipramine and metapramine was evaluated on oxotremorine induced trembling in the mouse as well as on contractions of the isolated guinea pig ileum induced by electrical stimulation of the mesenteric plexus. The ED 50 and IC 50 which expressed the anticholinergic activity of these substances, were found to be identifically distributed for both methods. Activity, in decreasing order was found to be: atropine much greater than imipramine greater than clomipramine greater than metapramine. There was a good correlation between results from the two methods (r = 0.97). The method using the stimulated guinea pig ileum would therefore seem suitable for characterisation of potential anticholinergic activity of a molecule.     

Decreased caloric intake in normal-weight patients with bulimia: comparison with female volunteers

Patients with bulimia (binge-purge syndrome) frequently complain that they consume a very restrictive diet to avoid gaining weight. To investigate this claim, 23 hospitalized bulimic patients were assessed daily for body weight, caloric intake, macronutrient diet content, activity measures, and body composition estimates during weight-stable periods. Bulimic patients ate fewer kilocalories per kilogram body weight (22.1 +/- 4.6 kcal/kg) than did age-matched normal women (29.7 +/- 6.5 kcal/kg) but had similar activity levels and body composition. Clinical variables, such as history of laxative abuse, anorexia, or obesity, and physiological characteristics, such as body weight, activity level, or dietary content, could not account for this difference in caloric consumption. Bulimic patients tended to eat a diet lower in fat and higher in protein than did control subjects. These results agree with observations of increased efficiency of caloric utilization in obese patients and support patient complaints of a tendency to gain weight easily.     

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.     

Failure of ivalon to provide permanent hepatic arterial occlusion

Ivalon (polyvinyl alcohol) is a commonly used embolic agent, generally considered to be permanent. In a patient with the carcinoid syndrome, embolization of hepatic metastases with Ivalon failed to produce permanent occlusion, and recurrent tumor was supplied by many of the same small arteries identified on the original arteriogram. Occasionally, Ivalon may have only a temporary occlusive effect. A possible explanation for this phenomenon is proposed.     

Hernia through the foramen of Winslow: a complication of cholecystectomy. A case report

In 151 years since first described, there have been 112 reported cases of hernia through the foramen of Winslow (HFW). All thus far have described HFW as a primary entity. The case reported appears to be unique with HFW as a surgical complication. HFW is the least common of internal hernias. The primary symptom is pain referred from the herniated organ and the hepatoduodenal ligament. An interesting sign is that the patient is found curled up or stooped over for pain relief. Anatomic factors implicated in HFW are an enlarged epiploic foramen, a floppy cecum and ascending colon, or abnormal length of small bowel mesentery. Tension on these structures causes pain with the torso extended. Distention of bowel in the lesser sac mimics gastric obstruction. Organs herniated are: small bowel (63%); cecum, ascending colon, and terminal ileum (30%); and transverse colon (7%). Of 25 cases reported since 1966, cecal herniation comprised two-thirds. The diagnosis may be made radiologically and the treatment is surgical. The case and a review of the literature are presented with attention to the anatomy. Also provided are the signs and symptoms of this interesting and perplexing diagnosis.     

Predicting failure in polytetrafluoroethylene vascular access grafts for hemodialysis: a pilot study

In order to determine if serial, noninvasive evaluation of polytetrafluoroethylene (PTFE) vascular access grafts could identify a subgroup of patients at risk for thrombosis, the authors studied flow characteristics, using duplex ultrasonic scanning, in 18 hemodialysis patients with forearm loop grafts. On average, five examinations were performed per patient over the 10-month study period. Seven episodes of thrombosis occurred in six patients. The mean Doppler flow in grafts that subsequently thrombosed was significantly lower than in those that did not (544 +/- 218 ml/min versus 843 +/- 391 ml/min, p less than 0.001). The interval from last examination to thrombosis ranged from 13 to 58 days. At a defined cut-off flow of 450 ml/min, this test yielded a sensitivity of 83% and a specificity of 75% for episodes of thrombosis occurring within 2 to 6 weeks. The authors conclude that episodes of thrombosis in PTFE arm loop grafts are usually preceded by significantly lower Doppler-measured flow than grafts that do not thrombose and that it may be possible, by this means, to identify grafts at risk.