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C S Davis

Publications and source records attributed to C S Davis.

9 recordsLinked to original sources

A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer's disease. The Tacrine Collaborative Study Group.

BACKGROUND: In Alzheimer's disease, there is a marked decline in the function of cholinergic neurons in the brain. However, studies of treatment with cholinesterase inhibitors have produced conflicting results. We conducted a multicenter trial to evaluate whether the cholinesterase inhibitor tacrine (1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate) could improve cognition in patients with Alzheimer's disease. METHODS: Of 632 eligible patients with probable Alzheimer's disease, 215 improved while receiving tacrine during a preliminary crossover phase to determine responsiveness and the best dose. The 215 patients were randomly assigned to receive either placebo or their best dose of tacrine (10 or 20 mg four times a day) in a six-week, double-blind trial. The primary measures of efficacy were the cognitive subscale of the Alzheimer's Disease Assessment Scale and the Clinical Global Impression of Change scale; the secondary measures included the Mini-Mental State Examination and the assessment of the activities of daily living. RESULTS: At the end of the six-week trial, the patients receiving tacrine had a mean adjusted cognitive-subscale score of 30.3 (Alzheimer's Disease Assessment Scale) as compared with 32.7 in patients receiving placebo. This represents a smaller decline (by 2.4 points) in cognitive performance in the tacrine group (P < 0.001). There were no differences between the groups in their global-rating scores. The tacrine group had a significantly smaller decline in the activities of daily living. The results of the Mini-Mental State Examination favored tacrine, but the differences were small and not statistically significant (a score of 16.0 with tacrine vs. 15.3 with placebo; P = 0.08). Gastrointestinal symptoms, elevation of aminotransferase levels, and headache were the most frequent side effects; all could be reversed by reducing the dose or discontinuing treatment. CONCLUSIONS: In this short-term study in patients with Alzheimer's disease who were selected for apparent responsiveness to tacrine, treatment with tacrine resulted in a statistically significant reduction in the decline of cognitive function, although this reduction was not large enough to be detected by the study physicians' global assessments of the patients.

Activities of Daily Living

The measurement of phosphatidate phosphohydrolase in human amniotic fluid.

Phosphatidate phosphohydrolase (EC 3.1.3.4) activity can be found in late gestational human amniotic fluid and is thought to originate in type II alveolar cells of the fetal lungs where it plays an important role in lung surfactant synthesis. In the present study, phosphatidate phosphohydrolase activity was detected and characterized in a 105 000 X g pellet of amniotic fluid using either [32P]phosphatidate or a water-soluble analog, 1-O-hexadecyl-rac-[2-(3)H]glycerol 3-phosphate as substrate. With either substrate, enzyme activity was optimal at pH 6.0. The soluble analog was hydrolyzed with a Km value of 163 micrometer and a V of 30 nmole/min per mg of protein, and offered several advantages over phosphatidate as a substrate for assaying phosphatidate phosphohydrolase in amniotic fluid. Using the synthetic analog, phosphatidate phosphohydrolase activity was measured in the 700 X g supernatant fraction of 30 human amniocentesis samples and compared with another index of fetal lung maturity, the phosphatidylcholine/sphingomyelin ratio. The results suggest that the new phosphohydrolase assay may be clinically useful in the assessment of fetal lung development.

Amniotic Fluid

Synthesis and hypotensive activity of a series of 2-substituted 5,6-dimethoxyindazoles.

The synthesis and hypotensive activity in the dog of a series of 2-substituted 5,6-dimethoxyindazoles are reported. Structure-activity relationships for this class of compounds are discussed. Indazoles containing the diethylaminoethyl, 3-pyridyl, and hydroxyethyl functions in the 2-position were the most effective in lowering blood pressure for the longest times (greater than 270 min).

Animals

Antinauseant and antiemetic properties of bismuth subsalicylate in dogs and humans.

Laboratory and clinical investigations were carried out to determine the effectiveness of bismuth subsalicylate in allaying nausea by preventing the physical symptom of emesis. In normal conscious dogs, a bismuth subsalicylate formulation caused a dose-related reduction in the incidence of vomiting in response to an emetic dose of ipecac syrup. In normal human subjects, a bismuth subsalicylate suspension, unlike the placebo formulation, successfully subdued nausea and vomiting in 66.7 and 80% of the subjects, respectively, in response to ipecac syrup. Both findings demonstrate that bismuth subsalicylate can provide antiemetic action and that the decreases in the occurrence of emesis in humans and dogs parallels the decrease in nausea found in humans and the nausea suspected to occur prior to emesis in dogs.

Adult

Multiple benign ureteral fibrous polyps.

Two cases of benign polyps of the ureter are reported with emphasis on the uroradiological features and methods of evaluation in the diagnosis of benign mesodermal tumors of the ureter. The apparently excellent results from conservative surgery make the recognition and preoperative roentgenologic diagnosis of this entity mandatory.

Adult