Acidic epinephrine analogues derived from 1H, 3H-2,1,3-benzothiadiazole 2,2-dioxide and from trifluoromethanesulfonanilide. A new synthesis of 1H,3H-2,1,3-benzothiadiazole 2,2-dioxide.

Treatment of N,N'-dibenzyl-1,2-diaminobenzene (2) successively with thionyl chloride and then m-chloroperbenzoic acid gave N,N'-dibenzyl-1H,3H-2,1,3-benzothiadiazole 2,2-dioxide (4), which gave (via routes analogous to standard epinephrine syntheses) four bicyclic catecholamine analogues 7a-d. Hydrogenolysis of 4 yielded the parent heterocycle 5 in the first practicable synthesis avoiding expensive sulfamide (Scheme I). The trifluoromethanesulfonamidoacetophenones 8m and 8p on similar elaboration gave triflanilide catecholamine analogues 14m, 14p,17m, and 17p (Scheme II). 4,4'Dimethoxybenzhydrylamine (15) is recommended for the regiospecific synthesis of primary amines from epoxides (Scheme II). Series 7,14, and 17 were inactive in animal cardiovascular screens. Selected compounds were also screened in bronchodilator and in in vitro dopamine-, clonidine-, and prazosin-receptor binding assays as appropriate; again no activity was observed. Steric lipophilicity, and acidity factors are discussed, and the inactivity is ascribed to the high acidity of both systems (pKa approximately equal to 4).

Compounds with gastric antisecretory activity. 1. Phenoxyalkylamines.

A series of 0-alkylphenoxyalkylamines, derived from classical H1 antagonists, has been found to inhibit histamine-induced gastric acid secretion. The most potent compound was trans-1-[2[2-[2-(1-adamantyl)vinyl] phenoxy] ethyl]pyrrolidine (54). The 0-acylphenol 23 required for the preparation of 54 was obtained by the novel reaction of 1-bromoadamantane (21) with 4-hydroxycoumarin (20) using diethyl phosphonate as solvent. The product 22 was then hydrolyzed under basic conditions to give 23 in high yield. 54 was not an H2 antagonist and its mode of action remains unknown. The compound had no significant anticholinergic, antiinflammatory, anticonvulsant, sedative, or H1-antihistaminic activity.

Studies on the transmission of viral disease via the CO2 laser plume and ejecta.

While recent reports have noted the presence of viral DNA sequences in the laser plume, no significant effort has been made to study transmission of the virus in vivo via airborne laser debris. Studies were undertaken to identify potential hazards to operating room occupants in gynecologic laser surgery. ACO2 laser in the continuous wave mode using a power density of 666 W/cm2 was fired through a 5-cm metal cylinder at virus-infected tissues. Airborne particulate debris, 100-200 microns, was removed from the cylinder's inner surfaces. In one instance, deposition of the debris was found on the surgeon's eyeglasses 1 m from the site of impact despite the use of a smoke evacuator. The first set of studies involved confirmed human papillomavirus (HPV) lesions of the human female lower genital tract. Specimens were collected for electron microscopy and Southern Blot viral hybridization. Additional cervical electron microscopy specimens were recovered from the speculum during pulsed CO2 laser treatment at 13 W average power during conization. Electron microscopy of the vulvar debris revealed only anucleate keratinized squamous epithelial cells. Cervical specimens demonstrated similar cells with nearly instantaneous vaporization of intracellular water and apparent condensation of cellular carbon. HPV Southern Blot testing revealed insufficient quantities of DNA for that technique. The second set of studies involved bovine papillomavirus lesions from dairy cattle. The debris was transmitted to susceptible animals. The bovine studies failed to demonstrate the transmission of disease in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Dealing with border issues the primary healthcare way.

Border issues are commonly conceptualised as concerns about inequities in health care for people living near State boundaries or borders. This paper examines how border issues have been addressed in the implementation of primary healthcare at the community level. The paper focuses on the implementation of primary healthcare principles in two towns, Wallangarra in Queensland and Jennings in New South Wales. The primary healthcare approach employed by Stanthorpe Health Services addressed border issues by providing the residents of Wallangarra and Jennings with equitable access to health service provision. The structure of health service delivery, the funding differences in each State and the impact of State policies on the residents of these two towns are discussed. The paper demonstrates how application of primary healthcare principles has reduced the impact of some of the border issues faced by the residents of Wallangarra and Jennings.