Synthesis, in vitro acetylcholine-storage-blocking activities, and biological properties of derivatives and analogues of trans-2-(4-phenylpiperidino)cyclohexanol (vesamicol)

Eighty-four analogues and derivatives of the acetylcholine-storage-blocking drug trans-2-(4-phenylpiperidino)-cyclohexanol (vesamicol) were synthesized, and their potencies were evaluated with the acetylcholine active-transport assay utilizing purified synaptic vesicles from Torpedo electric organ. The parent drug exhibits enantioselectivity, with (-)-vesamicol being 25-fold more potent than (+)-vesamicol. The atomic structure and absolute configuration of (+)-vesamicol were determined by X-ray crystallography. The absolute configuration of (-)-vesamicol is 1R,2R. Structure-activity evidence indicates that (-)-vesamicol does not act as an acetylcholine analogue. Alterations to all three rings can have large effects on potency. Unexpectedly, analogues locking the alcohol and ammonium groups trans-diequatorial or trans-diaxial both exhibit good potency. A potent benzovesamicol family has been discovered that is suitable for facile elaboration of the sort useful in affinity labeling and affinity chromatography applications. A good correlation was found between potencies as assessed by the acetylcholine transport assay and LD50 values in mouse.     

Reflex sympathetic dystrophy syndrome

Reflex sympathetic dystrophy syndrome is a devastating disease that is difficult to diagnose and treat. Presented here is a review of the literature explaining its clinical and radiographic findings, pathogenesis, diagnosis, and treatment modalities.     

Single-unit responses of serotonergic dorsal raphe nucleus neurons to environmental heating and pyrogen administration in freely moving cats

Single-unit activity of serotonergic neurons in the dorsal raphe nucleus was examined in response to environmental heating and pyrogen-induced fever in freely moving cats. In the heating study, ambient temperature was rapidly raised from a baseline of 25 degrees to 43 +/- 1 degrees C and maintained at this level for 2 h. Cats displayed hyperthermia, intense panting, and signs of heat stress, however, the discharge rate of serotonergic neurons of the dorsal raphe nucleus was not significantly different from baseline at any time during heat exposure. Similarly, the activity of these neurons was not significantly altered at any time during an approximately 6-h long febrile response induced by the synthetic pyrogen muramyl dipeptide (50 micrograms/kg, i.v.). These results indicate that serotonergic unit activity in the dorsal raphe nucleus is not related to either the activation of behavioral or physiological mechanisms underlying heat defense, or to alterations in thermoregulatory mechanisms during the febrile response to exogenous pyrogen. Furthermore, because these neurons do not respond to an elevation in body temperature induced by either ambient heating or pyrogen, they do not appear to be directly temperature-sensitive. These results do not support a specific role for serotonergic neurons of the dorsal raphe nucleus in thermoregulation.     

Behavior management of aggressive sequela after Reye's syndrome

This study describes the use of behavior management procedures to reduce the occurrence of severe behavioral sequela in a 14-year-old, post-Reye's syndrome male. Prior to intervention the client exhibited severe self-injurious, hyperaggressive, and food refusal behaviors that precluded any opportunities for rehabilitation, placed him at severe medical risk, and made him a candidate for institutional placement. With contingent restraint, in vivo desensitization, and reinforcement contingencies it was possible to control these behaviors and begin intensive rehabilitation. Subsequently, the client returned to his family and community day school for the severely handicapped where he remains five years later.     

Community attitudes towards performing cardiopulmonary resuscitation in Western Australia.

OBJECTIVE: to determine the attitudes of the Western Australian community towards performing cardiopulmonary resuscitation, and the factors affecting these attitudes. METHODS: telephone survey of a randomly selected sample of people from suburban Perth and rural Western Australia; practical assessment of a sub-sample of volunteers from those surveyed, to correlate survey answers with practical skills. RESULTS: of 803 people surveyed, the majority (90.7%) definitely would give mouth-to-mouth ventilation to a friend or relative, but less than half (47.2%) would to a stranger. The reluctance was mostly (56%) because of health and safety concerns, particularly related to HIV infection. Higher percentages of people would definitely provide cardiac massage for a friend or relative (91.4%) or stranger (78.1%). People were more likely to give mouth-to-mouth and cardiac massage if they had been trained in cardiopulmonary resuscitation (CPR), trained several times, trained recently, and used their CPR skills in real life. There were no significant differences between city and country people in whether they would provide CPR, but older people were less willing to provide mouth-to-mouth or cardiac massage. On practical assessment of 100 volunteers, there were significant errors and omissions in airway assessment, mouth-to-mouth resuscitation and cardiac massage. Volunteers with better practical scores were more prepared to provide CPR. DISCUSSION: our results indicate a significant reluctance of the Western Australia public to perform mouth-to-mouth, except to a friend or relative. Earlier CPR training, practice and use seemed to diminish this reluctance. Practical CPR skills were not well executed. Those with better skills were less reluctant to use them. We recommend increasing CPR training in the community, greater frequency of refresher courses and public education on the risks of CPR to improve rates of bystander CPR.