Biomedical subjects
Publications and source records attributed to B E Evans.
The first nonpeptide antagonists of the neurohypophyseal hormone, oxytocin (OT) are described. Derivatives of the spiroindenepiperidine ring system, these compounds include L-366,509, an orally bioavailable OT antagonist with good in vivo duration. The potential use of these agents for treatment of preterm labor and their significance as new nonpeptide ligands for peptide receptors are discussed.
Twenty four patients with the vulvar vestibulitis syndrome formed the basis of this clinicopathological study. Entry dyspareunia was the constant presenting complaint and vestibular erythema with acute superficial tenderness the invariable clinical finding. In our series there was a marked predominance of Caucasians, patients were most often of social classes I and II and most frequently in the third decade. The results of laboratory investigation revealed that this syndrome has a diverse range of potential aetiologies including vulval infections, dysplasia and in one instance acute vasculitis.
Widespread distribution of receptors for the peptide hormones cholecystokinin (CCK) and gastrin in the gut and in the CNS suggests therapeutic potential for selective antagonists of these hormones. Discovery of the natural product Asperlicin provided a new class of non-peptidal CCK antagonists, but oral bioavailability in this class remained elusive. With Asperlicin as a guide, the new, selective, orally bioavailable, high affinity CCK-A antagonist, MK-329 (L-364,718; Devazepide) and CCK-B/gastrin antagonist, L-365,260 have been developed. Biological profiles of these compounds are presented and results of early clinical evaluation of MK-329 are described. The significance of these agents as models for development of non-peptidal ligands for other receptors are briefly summarized.
Tifluadom, a kappa-opioid agonist and cholecystokinin-A (CCK-A) receptor antagonist, was utilized as a model to prepare a series of 2-(aminomethyl)- and 3-(aminomethyl)-1,4-benzodiazepines. These compounds were tested in vitro as inhibitors of the binding of [125I]CCK to rat pancreas and guinea pig brain receptors. All compounds with IC50's less than 100 microM proved to have greater affinity for the CCK-A receptor, with the most potent analogue, 6e, having an IC50 of 0.16 microM. The benzodiazepines described in this study are simultaneously CCK-A and opioid receptor ligands. The ramification of this dichotomy on current concepts of peptide hormone action are discussed. These results further demonstrate the versatility of the benzodiazepine core structure for designing nonpeptide ligands for peptide receptors and the ability to fine-tune the receptor interactions of these benzodiazepines by appropriate structure modifications.
A microcystalline collagen hemostat effected rapid hemostasis in dental extractions for a hemophilic patient with a significant level of inhibitor where preoperative transfusion of deficient factor was contraindicated. It appears that MCH can be used safely and effectively for a variety of oral procedures. In addition to its hemostatic properties, the ease with which it can be handled and its adherence make it adaptable for use in locations of limited access. In comparison with currently used materials, such as gelatin foam, it may have wider application and may be of greater benefit in achieving hemostasis in procedures in the oral cavity.
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Routine dental procedures do not generally involve bleeding; consequently, there is no contraindication to routine dental treatment for hemophiliacs. Preventive dentistry is vital to the younger hemophiliac patient world-wide; older hemophiliacs may require extensive treatment to restore mouths that have been neglected. Surgical dental procedures may be performed for hemophiliacs, but they must be judiciously coordinated by the dental and medical team. The facilities and treatment available will determine the feasibility of treating such patients in the hospital or on an outpatient basis.
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Hemophilic patients must be thought of as special patients. Since routine dental procedures, however, do not usually involve bleeding, there is no contraindication to general dental treatment for hemophiliacs. Aspirin-containing compounds should never be prescribed. Caution must be used with local anesthetic block techniques. Preventive dentistry is vital to the younger hemophiliac; older hemophiliacs may require extensive treatment to restore mouths that have been neglected for years. Surgical dental procedures are now considered possible for hemophiliacs and may be performed on an outpatient basis, but they must be judiciously coordinated by the dental and medical team.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.