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)     

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.     

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.     

Experimental induction of anxiety. The case of carbon dioxide

This paper reviews recent developments in the experimental approach to panic anxiety. Inhalation of carbon dioxide appears to trigger panic attacks in panic disorder patients and agoraphobics. The biological and psychopathological implications of this finding are discussed in the light of recent data on experimental pharmacology of anxiety.     

Increased risk of cancer at multiple sites after gastric surgery for peptic ulcer.

Of 5018 patients who had undergone gastric surgery at St James Hospital, Balham, at least 25 years ago, death certificates have been received for 2768, whilst 1746 patients are still alive and are flagged (Office of Populations, Censuses and Surveys (OPCS) will notify us of their death and its cause) and only 504 could not be traced. Mortality from cancers of various organs has been determined using a 'years at risk' calculation in five year bands. There was no increase in mortality risk from any cancers during the first 15 postoperative years, but from 20 years after operation there was a significant excess risk not only of cancer of the stomach (4.5-fold), but also of the large bowel (1.6-fold), bronchus (3.9-fold), pancreas (4.0-fold), biliary tract (9.1-fold), oesophagus (2.3-fold), bladder (2.4-fold), breast (4.0-fold), and cancer of all sites (3.3-fold). These findings are consistent with the production in the operated-upon stomach of circulating carcinogens with a 20 year latency period.     

Scanning Electron Microscopic Observations on the Epithelium of the Human Prostatic Urethra

The human prostatic urethra has been investigated by means of scanning electron microscopy. On the posterior wall of the urethra, the seminal colliculus with the orifices of the ejaculatory ducts is clearly detectable. The upper portion of the prostatic urethra shows a typical transitional epithelium with large superficial cells of a ruffled appearance. In the lower portion of the organ (underneath the openings of the ejaculatory ducts), the apical pattern of the cells varies considerably. Four main aspects are recognizable: apices provided with microvilli, dome-shaped apices with an almost smooth surface, large apices with labyrinthic microplicae and ciliated apices. Also, apices showing intermediate characteristics can be noted. The functional significance of the morphological patterns as well as the possibility of a transition among the various types of surface structures are discussed.