Effects of ranitidine, given t.d.s., on intragastric and oesophageal pH in patients with gastrooesophageal reflux

The purpose of this study was to determine the effects of 150 mg ranitidine, 300 mg ranitidine or placebo, administered every 8 h, on gastro-oesophageal pH and heartburn parameters in reflux patients. Twelve symptomatic reflux patients received each of the three treatments in a randomized, double-blind, crossover fashion. Intragastric and oesophageal pH were monitored continuously for a 24 h period. Meals were standardized, consumed at set times and patients were allowed to recline and sleep from 23.00 hours until 06.00 hours only. The gastric record was analysed for the percentage of time that the pH was greater than or equal to 4. The oesophageal record was analysed for acid contact time (percentage time (%) pH less than or equal to 4.0) and reflux episode frequency. Finally, patients recorded each new episode of heartburn and graded daytime heartburn severity at the end of each hour. Ranitidine increased the median (%) time that the intragastric pH remained at or above 4, from 4.5 (placebo) to 33.9% (150 mg dose) and 33.3% (300 mg dose). Ranitidine dose-dependently reduced the median 24-hour oesophageal acid contact time from 13.3% (placebo) to 6.8% (150 mg dose) and 2.5% (300 mg dose). The 300 mg dose significantly reduced daytime heartburn episode frequency and severity while the 150 mg dose reduced heartburn severity only. We conclude that 150 and 300 mg doses of ranitidine administered every 8 h have major, sometimes dose-dependent effects on the objective parameters and symptoms of gastro-oesophageal reflux.     

The tobacco use research program at Oregon Research Institute

The research program at ORI deals with both adolescent and adult tobacco use and is guided by a behavioral framework which emphasizes the role of the social context in tobacco use onset, maintenance and cessation. Growing appreciation of the importance of social context variables, combined with an emerging recognition of the need for a public health rather than clinical perspective on tobacco use, have led to a focus on interventions in larger social systems such as schools, worksites, health care plans, and communities. This research requires attention to the science of behavior change at both the individual and organizational levels.     

Protection from gastrointestinal side-effects by azapropazone by its incorporation into a glucose—sodium acid citrate formulation

Addition of glucose and sodium citrate to azapropazone, in proportions of 1:1:1 by weight reduced gastric mucosal damage in rats and there was a trend towards reduction in radiolabelled faecal red cell loss in human volunteers compared with that with azapropazone alone. The glucose and citrate did not affect the pharmacokinetics of azapropazone, or its therapeutic efficacy. While no difference was observed in endoscopic injury and in symptomatic gastrointestinal complaints in a multicentre comparison in rheumatic patients, a striking reduction in symptoms was observed in those patients with a history of severe gastrointestinal intolerance to non-steroidal anti-inflammatory drugs.     

Gene Probe Analysis in an Informative Family with Multiple Endocrine Neoplasia Syndrome Type 2A (MEN 2A). Improvement in Carrier Risk Estimation

Gene probe analysis of the MEN 2A locus on chromosome 10 hasbeen undertaken using the markers TB10.163, RBP 3 and TB14.34in a large kindred with familial medullary thyroid carcinomas,with or without phaeochromocytomas or primary hyperparathyroidism.A maximum LOD score of 2.97 gave strong evidence of close linkagewith zero recombination. For 12 members of the family so far not known to be affectedby any form of the disease the estimated risk of carrying thegene has been considerably decreased in all but one, whose riskhas been greatly increased.     

Three-dimensional structure of bradykinin in SDS micelles

The conformational properties of bradykinin in five molar excess sodium dodecyl sulfate (SDS) micelles have been examined by two-dimensional nuclear magnetic resonance (NMR) techniques at 500 MHz. Detailed structural information for bradykinin in SDS was obtained from quantitative 2-D nuclear Over-hauser enhancement (n.O.e.) analyses, distance geometry, and restrained molecular mechanics and dynamics calculations. The conformation of bradykinin in SDS micelles, as determined by these methods, is characterized by a β-turn-like structure at residues 6–9. A detailed comparison of the structures derived from distance geometry and restrained molecular mechanics and dynamics is also presented.     

Synthesis of a potent agonist of substance P by modifying the methionyl and glutaminyl residues of the C-terminal hexapeptide of substance P

Analogues of [Orn⁶]-SP_6-11 have been synthesized in which the Met¹¹ residue is replaced by glutamate γ-alkylesters. These analogues were tested in three in vitro preparations representative of NK-1, NK-2, and NK-3 receptor types. Substitution of the SCH₃ group of the Met¹¹ side chain by a COOR (R = methyl, ethyl, n-propyl, n-butyl, cyclohexyl) group results in analogues which are full agonsists in NK-1 and NK-2 preparations but show little agonist activity in the NK-3 preparation. When the SCH₃ group is replaced by a t-butyl ester group and the resulting analogue is a full agonist in all the above preparations and more active than the parent hexapeptide and SP-OCH₃ at NK-1 receptors. It is concluded that for activity at NK-1 receptors methionine can be replaced by γ-t-butyl glutamate without loss of activity, whilst at NK-2 and NK-3 receptors the above substitution increases the activity of [Orn₆]-SP_6-11. Other γ-alkyl esters of the glutamic acid reduce its biological activity.