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Biomedical subjects

Gary G Kay

Publications and source records attributed to Gary G Kay.

7 recordsLinked to original sources
PubMed2005

Antimuscarinic agents: implications and concerns in the management of overactive bladder in the elderly.

BACKGROUND: Overactive bladder (OAB) is a widespread problem that has a negative effect on quality of life, particularly among the elderly. Antimuscarinic agents are the only drug class with broad, accepted efficacy in the treatment of OAB. Their clinical usefulness, however, is limited by dose-dependent adverse effects. In the elderly, the most serious of these is central nervous system (CNS) dysfunction, including cognitive impairment. OBJECTIVE: This article examines currently available antimuscarinic agents for the treatment of OAB in terms of their likelihood of causing CNS dysfunction by crossing the blood-brain barrier (BBB) and blocking muscarinic type 1 (Ml) receptor sites in the brain. METHODS: Pertinent studies were selected from a comprehensive review of the OAB literature with a focus on muscarinic receptor-associated mechanisms leading to CNS adverse effects and their potential impact on elderly patients. MEDLINE was searched for articles published in the past 10 years, and additional articles were obtained from the reference lists of identified publications. Also searched were abstracts of recent meetings of the International Consultation on Incontinence, International Continence Society, American Urological Association, and European Association of Urology. RESULTS: Antimuscarinic agents control involuntary detrusor muscle contractions through cholinergic blockade at the muscarinic receptors. The prevalence of OAB is highest in the elderly, the population most likely to be taking multiple anticholinergic medications and most vulnerable to the CNS adverse effects of these agents. Nonselective antimuscarinic agents that bind to the Ml receptor are most likely to cause significant cognitive adverse effects compared with the more selective antimuscarinic agents for the treatment of OAB. CONCLUSIONS: When considering use of an antimuscarinic agent for the treatment of OAB in elderly patients, prescribers should routinely consider the agent's receptor selectivity and ability to cross the BBB. The medical history should include all current medications that may contribute to the anticholinergic burden and cognitive impairment. Patients and caregivers should be educated to recognize anticholinergic adverse effects.

Aged↗
PubMed2005

Pharmacodynamic effects of darifenacin, a muscarinic M selective receptor antagonist for the treatment of overactive bladder, in healthy volunteers.

OBJECTIVE: To evaluate the pharmacodynamic effects of darifenacin (a muscarinic M(3) selective receptor antagonist) and dicyclomine (an M(1) selective receptor antagonist) in healthy male volunteers. SUBJECTS AND METHODS: In this double-blind, four-way crossover study, 27 healthy men (aged 19-44 years) were randomized to receive darifenacin 7.5 mg or 15 mg once daily, dicyclomine 20 mg four times daily or matching placebo. Each 7-day treatment period was separated by a 7-day washout. Multiple assessments of cognitive function, quantitative electroencephalogram (EEG) recordings, salivation, visual nearpoint, heart rate and heart rate variability were made on day 7 in each treatment period. RESULTS: Compared with placebo, neither dose of darifenacin affected cognitive function, whereas dicyclomine impaired performance on five of the 12 variables 2 h after dosing; simple reaction time (P = 0.009), speed of numeric (P = 0.012) and spatial (P = 0.048) working memory, and speed (P = 0.04) and sensitivity (P = 0.03) of picture recognition. These cognitive changes were accompanied by slowing of the EEG for dicyclomine. Darifenacin showed no clinically relevant effect on EEG. Darifenacin 7.5 and 15 mg once daily did not differ from placebo in effects on visual nearpoint, heart rate or heart rate variability. By contrast, dicyclomine significantly increased the maximum visual nearpoint, decreased heart rate and increased heart rate variability, relative to placebo. Both agents decreased salivary flow rate vs placebo. Treatment-related adverse events were comparable in all groups, the most common being dry mouth; none led to treatment discontinuation. CONCLUSIONS: Darifenacin did not affect cognitive, cardiac or visual function in healthy volunteers, a profile that may reflect its relative M(3) receptor selectivity and M(1)/M(2) sparing properties.

Adult↗
PubMed2005

Antimuscarinic drugs for overactive bladder and their potential effects on cognitive function in older patients.

Antimuscarinic agents are the predominant pharmacological treatment for patients with overactive bladder (OAB). These drugs are thought to act primarily through antagonism at muscarinic M3 receptors located at neuromuscular junctions in the human bladder detrusor muscle. Several of these drugs have been shown to be efficacious in ameliorating the symptoms of OAB in older patients, but most currently available agents lack selectivity for the M3 receptor subtype, and interaction with other muscarinic receptor subtypes throughout the body may adversely affect a variety of physiological functions and result in unwanted side effects, including cognitive dysfunction. With the recent availability of antimuscarinic agents that show increased selectivity for M3 receptors relative to other muscarinic subtypes, an invitational expert panel meeting was convened to review not only the mechanisms by which antimuscarinic agents could affect cognitive function, but also the published literature on cognitive adverse events. A review of the literature shows that the cholinergic system in the central nervous system (CNS) exerts a major influence on cognitive processes, in particular memory via M1 cholinergic receptors. In addition, recent evidence suggests a role for M2 receptors in mediating cognitive function. Thus, cognitive dysfunction (including memory loss) during treatment with nonselective antimuscarinic agents for OAB is of growing concern, particularly in older patients and those with mild cognitive impairment or dementia. Increased blood-brain barrier permeability, which can occur with advanced age and certain comorbidities, may also facilitate CNS access of antimuscarinic agents (regardless of their physiochemical properties) and add to antimuscarinic burden. On the basis of available evidence, antimuscarinic agents with selectivity for M3 over M1 and M2 receptors, limited CNS penetration, or both may therefore offer a favorable balance of efficacy in treating OAB together with a reduced risk of adverse cognitive events in the older population.

Age Factors↗
PubMed2004

Human exposure to the jet fuel, JP-8.

INTRODUCTION: This study investigates anecdotal reports that have suggested adverse health effects associated with acute or chronic exposure to jet fuel. METHODS: JP-8 exposure during the course of the study day was estimated using breath analysis. Health effects associated with exposure were measured using a neurocognitive testing battery and liver and kidney function tests. RESULTS: Breath analysis provided an estimate of an individual's recent JP-8 exposure that had occurred via inhalation and dermal routes. All individuals studied on base exhaled aromatic and aliphatic hydrocarbons that are found in JP-8. The subject who showed evidence of the most exposure to JP-8 had a breath concentration of 11.5 mg x m(-3) for total JP-8. This breath concentration suggested that exposure to JP-8 at an Air Guard Base is much less than exposure observed at other Air Force Bases. This reduction in exposure to JP-8 is attributed to the safety practices and standard operating procedures carried out by base personnel. The base personnel who exhibited the highest exposures to JP-8 were fuel cell workers, fuel specialists and smokers, who smoked downwind from the flightline. DISCUSSION: Although study-day exposures appear to be much less than current guidelines, chronic exposure at these low levels appeared to affect neurocognitive functioning. JP-8-exposed individuals performed significantly poorer than a sample of non-exposed age- and education-matched individuals on 20 of 47 measures of information processing and other cognitive functions.

Adult↗
PubMed2000

Functional magnetic resonance imaging reflects changes in brain functioning with sedation.

Functional magnetic resonance imaging (fMRI) studies have demonstrated localized brain activation during cognitive tasks. Brain activation increases with task complexity and decreases with familiarity. This study investigates how sleepiness alters the relationship between brain activation and task familiarity. We hypothesize that sleepiness prevents the reduction in activation associated with practice. Twenty-nine individuals rated their sleepiness using the Stanford Sleepiness Scale before fMRI. During imaging, subjects performed the Paced Auditory Serial Addition Test, a continuous mental arithmetic task. A positive correlation was observed between self-rated sleepiness and frontal brain activation. Fourteen subjects participated in phase 2. Sleepiness was induced by evening dosing with chlorpheniramine (CP) (8 mg or 12 mg) and terfenadine (60 mg) in the morning for 3 days before the second fMRI scan. The Multiple Sleep Latency Test (MSLT) was also performed. Results revealed a significant increase in fMRI activation in proportion to the dose of CP. In contrast, for all subjects receiving placebo there was a reduction in brain activation. MSLT revealed significant daytime sleepiness for subjects receiving CP. These findings suggest that sleepiness interferes with efficiency of brain functioning. The sleepy or sedated brain shows increased oxygen utilization during performance of a familiar cognitive task. Thus, the beneficial effect of prior task exposure is lost under conditions of sedation. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗
PubMedDate not supplied

Guidelines for the psychological evaluation of air crew personnel.

Air crew personnel (i.e., pilots, flight attendants, and air traffic controllers) are subjected to intense psychological and physical stress. Recent terrorist attacks in the U.S., the increased frequency of unruly passenger incidents, and the instability of the aviation industry have exacerbated air crew stress. In addition, common neuropsychiatric conditions (e.g., alcoholism, head trauma, HIV, depression) can impair operational fitness. This article discusses the aviation medical certification process and proposes guidelines for psychological evaluation, including: qualifications of providers, selection of psychological and neuropsychological tests, and the elements of a comprehensive, unbiased examination process.

Aerospace Medicine↗