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K Cheshire

Publications and source records attributed to K Cheshire.

5 recordsLinked to original sources
PubMed2001

Recruitment of participants for the Estrogen Replacement and Atherosclerosis (ERA) trial. a comparison of costs, yields, and participant characteristics from community- and hospital-based recruitment strategies.

This paper documents recruitment for the Estrogen Replacement and Atherosclerosis trial, a multicenter, placebo-controlled, double-blind angiographic trial of the effects of opposed and unopposed estrogen on coronary atherosclerosis in postmenopausal women (average scheduled duration of follow-up 3.2 years). We compare costs, yields, and participant characteristics between community-based and hospital-based recruitment strategies. We further compare community-based enriched sources (i.e., those that allowed self-selection or targeted women with known health characteristics) and nonenriched sources. Data gathered on potential participants include method of contact, clinical site, eligibility, completion of screening visits, and randomization rates. Demographic data on participants include age, race, education, marital status, and income. Self-reported health status, smoking status, lipid level, ejection fraction as well as history of chest pain, hypertension, and diabetes were recorded at baseline. Recruitment costs were estimated from employee salaries and costs of screening tests and procedures. Yields were compared by clinical site and by method of contact. Enriched sources of recruitment yielded higher percentages of enrolled participants than nonenriched sources. Both types of source resulted in demographically similar participants. Costs of community-based recruitment were less than hospital-based recruitment; however, screening costs were higher. Overall, screening and recruitment averaged $2508 per randomized participant. Control Clin Trials 2001;22:13-25

Aged↗
PubMed2001

A spermine-coupled cholesterol metabolite from the shark with potent appetite suppressant and antidiabetic properties.

OBJECTIVE: We describe the pharmacological properties of a novel spermine-cholesterol adduct, MSI 1436 (3beta-N-1(spermine)-7alpha, 24R-dihydroxy-5alpha-cholestane 24-sulfate), which causes reversible suppression of food and fluid intake in mammals resulting in profound weight loss, not associated with other signs or symptoms of illness, and which exhibits antidiabetic properties in genetically obese mice. METHODS: Wild-type rodents and strains with genetic obesity were studied. Effects on food and fluid intake, body weight and composition were examined along with pharmacological and toxicological parameters. RESULTS: MSI-1436 induces profound inhibition of food and fluid intake in rats and mice, resulting in significant weight loss. MSI-1436 is active when introduced directly into the third ventricle of the rat, suggesting the compound acts on central targets. Pair-feeding studies suggest that MSI-1436 causes weight loss by suppressing food intake. Fluid intake is also profoundly reduced but animals remain normally hydrated and defend both water and electrolyte balance from parenteral administration. MSI-1436 is active in ob/ob, db/db, agouti and MC4 receptor knockout mice. MSI-1436 has been administered to ob/ob mice over a 4 month period via a regimen that safely controls body weight, glucose homeostasis and serum cholesterol levels. Following MSI-1436 treatment, db/db mice preferentially mobilize adipose tissue and hyperglycemia is corrected. CONCLUSION: A naturally occurring spermine metabolite of cholesterol, isolated from the dogfish shark, Squalus acanthias, has been identified that induces profound reduction in food and fluid intake in rodents in a setting where thirst is preserved and fluid and electrolyte homeostasis appears to be functioning normally. MSI-1436 probably acts on a central target involving neural circuits that lie downstream from the leptin and the MC4 receptors. Although long-term administration can be accomplished safely in mice, the utility of this compound as a potential human therapeutic awaits an analysis of its pharmacological properties in man.

Animals↗
PubMed1998

Squalamine inhibits angiogenesis and solid tumor growth in vivo and perturbs embryonic vasculature.

The novel aminosterol, squalamine, inhibits angiogenesis and tumor growth in multiple animal models. This effect is mediated, at least in part, by blocking mitogen-induced proliferation and migration of endothelial cells, thus preventing neovascularization of the tumor. Squalamine has no observable effect on unstimulated endothelial cells, is not directly cytotoxic to tumor cells, does not alter mitogen production by tumor cells, and has no obvious effects on the growth of newborn vertebrates. Squalamine was also found to have remarkable effects on the primitive vascular bed of the chick chorioallantoic membrane, which has striking similarities to tumor capillaries. Squalamine may thus be well suited for treatment of tumors and other diseases characterized by neovascularization in humans.

Animals↗
PubMed1992

Factors impairing daytime performance in patients with sleep apnea/hypopnea syndrome.

Patients with sleep apnea/hypopnea syndrome commonly demonstrate impaired daytime performance. In a prospective study, 29 patients with sleep apnea/hypopnea syndrome were assessed polysomnographically to determine the relationship of cognitive performance and daytime sleepiness with sleep disruption, hypoxemia, and mood. Deterioration of cognitive performance correlated significantly with increasing severity of nocturnal breathing irregularity, magnitude of nocturnal hypoxemia, and extent of sleep disruption. Multiple regression analysis identified frequency of apneas plus hypopneas and of arousal and the extent of nocturnal hypoxemia as the variables most strongly associated with cognitive deficits. Anxiety and depression also contributed to this impairment. Objective daytime sleepiness was not significantly associated with nocturnal variables. This study showed that the frequency of breathing irregularities and the extent of both sleep disruption and nocturnal hypoxemia are important in determining daytime function in patients with sleep apnea/hypopnea syndrome. All of these factors should be considered when deciding which patients require treatment.

Adult↗