Design and synthesis of piperidinyl piperidine analogues as potent and selective M2 muscarinic receptor antagonists.

Identification of a number of highly potent M2 receptor antagonists with >100-fold selectivity against the M1 and M3 receptor subtypes is described. In the rat microdialysis assay, this series of compounds showed pronounced enhancement of brain acetylcholine release after oral administration.

Diphenylsulfone muscarinic antagonists: piperidine derivatives with high M2 selectivity and improved potency.

Piperidine analogues of our previously described piperazine muscarinic antagonists are described. Piperidine analogues show a distinct structure-activity relationship (SAR) that differs from comparable piperazines. Compounds with high selectivity and improved potency for the M2 receptor have been identified.

An epidemic of corneal destruction caused by plasma gas sterilization. The Toxic Cell Destruction Syndrome Investigative Team.

Background: Toxic endothelial cell destruction (TECD) syndrome after intraocular ophthalmic surgery is rare and can result from exposure to a variety of toxins. During January 8 to 14, 1998, 6 patients developed TECD with corneal edema associated with unreactive or dilated pupils at Hospital A.

Methods: A case patient was any Hospital A patient with TECD within 24 hours after surgery during January 5 to 14, 1998 (epidemic period).

Unexpected corneal endothelial cell decompensation after intraocular surgery with instruments sterilized by plasma gas.

Purpose: Ten cases of unexpected corneal endothelial cell decompensation occurring after routine intraocular surgery using instruments sterilized with a new plasma gas protocol are described.

Design: A retrospective observational case series with 1 year of follow-up was conducted.

Results: All patients had corneal decompensation and nonreactive pupils after surgery.

In vivo autoradiography of [3H]SCH 39166 in rat brain: selective displacement by D1/D5 antagonists.

The purpose of this study was to examine the receptor occupancy of D1/D5 antagonists for D1-like dopamine receptors in rat brain using [3H]SCH 39166, a highly selective D1/D5 antagonist with low affinity for 5HT2 receptors. A single concentration of triated SCH 39166 was administered to rats, with or without competing doses of the Dl/D5 antagonist SCH 23390 and unlabeled SCH 39166. the D2-like antagonists haloperidol or the 5-HT, antagonist ketanserin.

Multistate outbreak of hemolysis in hemodialysis patients traced to faulty blood tubing sets.

Background: Hemolysis associated with hemodialysis is rare. The most frequent causes of hemodialysis-associated hemolysis are chemical contamination, heat, or mechanical injury of erythrocytes from occluded or kinked hemodialysis blood lines. When patients in three states developed hemolysis while undergoing hemodialysis between May 13 and 23, 1998, an investigation was initiated.

Intonation unit analysis of conversational discourse in closed head injury.

This study employed a modification of the intonation unit analysis for conversational discourse developed by Mentis and Prutting. The percentage of total intonation units produced within separate ideational categories was calculated for groups of closed head-injured and normal control subjects as well as the examiner. No significant differences were found between subject groups or the examiner's performance within the two groups.

SCH 57790: a novel M2 receptor selective antagonist.

As a decrease in cholinergic neurons has been observed in Alzheimer's Disease (AD), therapeutic approaches to AD include inhibition of acetylcholinesterase to increase acetylcholine levels. Evidence suggests that acetylcholine release in the CNS is modulated by negative feedback via presynaptic M2 receptors, blockade of which should provide another means of increasing acetylcholine release. Structure-activity studies of [4-(phenylsulfonyl)phenyl]methylpiperazines led to the synthesis of 4-cyclohexyl-alpha-[4-[[4-methoxyphenyl]sulfinyl]-phenyl]-1-piperazin eacetonitrile.

Sch 50971, an orally active histamine H3 receptor agonist, inhibits central neurogenic vascular inflammation and produces sedation in the guinea pig.

We studied the actions of Sch 50971, a novel histamine H3 receptor agonist, in an experimental neurogenic model of migraine and characterized its sedative and respiratory actions. Sch 50971 (i.v.

History of federal legislation in health professions educational assistance in dental public health, 1956-97.

Health professions education assistance in dental public health has been congressionally authorized in one form or another during the last four decades. The US Department of Health and Human Services (and its predecessor, the Department of Health, Education, and Welfare) has been a focal point for managing these federal programs. This report tracks the history of relevant national legislation, beginning in the 1950s with the Health Amendment Acts of 1956 and continuing most recently with the Health Professions Education Extension Amendments of 1992.

Dental public health for the 21st century: implications for specialty education and practice.

A panel of public health practitioners sponsored by the Health Resources and Services Administration met December 6-8, 1994, to examine current roles and responsibilities for dental public health workers and to recommend changes in education and training to meet challenges posed by an evolving health care system. Overall, at least the same number, if not more, dental public health personnel will be needed in the future. While some new roles were identified, the panel felt that only small numbers of personnel will be needed to fill these new roles.

Residency training in dental public health: assessment of status, needs, and issues.

The opportunities for public health training have declined over the years while the need for public health skills is likely to increase. This paper reports the results of a project, sponsored by the Health Resources and Services Administration, which answers the question of "how best to invest in the dental public health education system so as to fulfill the profession's responsibilities to protect and improve the oral health of individuals and society." An information base on dental public health education, practice, and specialization was developed from an extensive review of the literature and a survey of dentists concerning employment and practice requirements for public health dentists.

Obstacles to addressing professional misconduct.

The Ethical Principles exhort psychologists "to encourage ethical behavior by students, supervisees, employees, and colleagues, as appropriate" (American Psychological Association, 1992, p. 1599). In spite of a clear directive to attempt resolution of unethical conduct by colleagues, research indicates that satisfactory resolution or actual reporting of misconduct is infrequent.

Filling the gap: equity and access to oral health services for minorities and the underserved.

Family physicians and other primary care providers play a pivotal role in preventing oral disease, especially among minority and underserved populations who have limited access to dental services and poorer oral health status. Oral diseases/conditions, such as caries, baby bottle tooth decay, gingivitis, periodontitis, oral pharyngeal malignancies, and orofacial trauma, are prevalent and costly, yet largely preventable. Given their role in promoting and protecting overall health and their historical role in serving minority and underserved families, family physicians occupy a unique position to assure equity, access, and improvement in oral health for all Americans.

A military-civilian resource-sharing agreement.

A first-of-its-kind resource-sharing agreement between the US Department of Defense and a civilian hospital was undertaken with resounding success. This article discusses how Sacred Heart Medical Center, Spokane, Wash, and the 92nd Medical Group at Fairchild Air Force Base, Spokane, Wash, developed the project and accomplished the integration, which continues to benefit each organization.

General dentistry grant program: 1976-1996.

The federal general dentistry grant program supports the development of new programs and first-year positions in postdoctoral general dentistry (PGD) education. One hundred and fifteen institutions have participated in the grant program since awards were first made in 1978. The grant program assisted in establishing 59 new PGD programs and 560 new positions.

Advancing discourse on health promotion: beyond mainstream thinking.

Attention must be redirected toward health promotion as nursing evaluates the goal of health for all. Confusion regarding health promotion behavior is illustrated by terms with diverse meanings and uses. In a process of critical analysis, five multidisciplinary experts in health promotion responded to a survey targeting the distinction of health promotion, health promotion behavior, health protection behavior, disease prevention behavior, preventive health behavior, health behavior, and healthy lifestyle.

The assessment of limb apraxia: an investigation of task effects and their cause.

To test the effects of variations in the structure of tasks used to assess limb apraxia, eight tasks--differing in their modes of elicitation (tactile, verbal, visual, imitation) and/or types of movement elicited (transitive, intransitive, meaningless)--were administered to 25 carefully selected subjects with idiomotor limb apraxia. When standardized scores (based on the performance of 10 nonneurologically impaired control subjects) were used to measure the differences between tasks, no clinically significant task effects were found. Additional investigation was made of two causal hypotheses regarding the processes underlying limb apractic performance.

An investigation of a method of simplified scoring for the Kaufman Hand Movements test as a measure of limb apraxia.

A simplified, 3-category method for scoring the Kaufman Hand Movements test was devised to replace a previously used, more complex 21-category scoring method. The concurrent validity and diagnostic sensitivity of the rescored test as a measure of limb apraxia were investigated in a reanalysis of the test protocols of 23 aphasic adults. Using the Limb Apraxia Test as the criterion measure, a Pearson r of .

Impairments of discourse abilities and executive functions in traumatically brain-injured adults.

Preliminary findings from an ongoing investigation of the potential relationship between narrative discourse performance and executive functions in adults with traumatic brain injuries (TBI) are reported. Narrative stories were elicited from 32 adults with TBI. Stories were analysed at three levels: sentence production, intersentential cohesive adequacy, and story episode structure.

Measurement of narrative discourse ability in children with language disorders.

Narratives from three studies differing in subject pools, elicitation procedures, and story content were analyzed using seven variables hypothesized to measure a variety of language abilities used in narrative production. Two questions were addressed: (a) To what extent did multiple variables represent common factors? and (b) To what extent did these variables distinguish children with language disorder from their nondisordered peers? Results indicated that: (a) The seven variables represented two factors; Factor I measured global organization of content (i.e.

Concurrent validity of the Kaufman Hand Movement Test as a measure of limb apraxia.

The concurrent validity of the Kaufman Hand Movement Test as a measure of limb apraxia was investigated. For 23 adult aphasic subjects, a Pearson r of 0.84 was obtained between scores on this test and on the Limb Apraxia Test, a battery of tasks often used in the assessment of limb apraxia.

Characterization of the binding of SCH 39166 to the five cloned dopamine receptor subtypes.

Characterization studies were conducted on the five cloned dopamine receptor subtypes (D1-D5) using the novel D1-selective antagonist, SCH 39166, as well as other related benzazepines and dopaminergic agents. The results demonstrate that SCH 39166 exhibits saturable, high-affinity binding to the D1 and D5 receptors, but binds with low affinity to the D2, D3, and D4 receptors. In contrast, the D2 antagonist haloperidol showed low affinity for the "D1-like" receptors and high affinity for the "D2-like" receptors.