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PubMed2004

Stimulant and relaxant drugs combined with stimulant and relaxant information: a study of active placebo.

RATIONALE: The active placebo hypothesis states that placebo effects are potentiated when an active drug is administered. OBJECTIVE: This hypothesis was tested in an experiment where information about the effect of a drug was combined with administration of an active drug or placebo. METHODS: Information that a drug acted as a relaxant, a stimulant, or as a placebo was crossed with oral administration of a relaxant drug (700 mg carisoprodol), a stimulant drug (400 mg caffeine) or placebo (lactose) in healthy volunteers ( n=94). Dependent variables were subjective and physiological measures of arousal, as well as serum carisoprodol and caffeine levels. Data were collected from 15 to 280 min after administration of drug or placebo. RESULTS: Caffeine increased alertness, systolic and diastolic blood pressure, startle blink reflexes, and skin conductance responses. Subjects were calmer after carisoprodol, and heart rate was increased. There was a positive correlation between increased arousal and carisoprodol levels when stimulant information had been provided. However, this was only seen when carisoprodol levels were very low. There was no evidence that caffeine modulated the placebo response. CONCLUSIONS: Active placebo responses were seen only transiently when carisoprodol levels were low, and only in the subjective arousal data. Caffeine did not support active placebo responses. The overall findings did not favour the active placebo hypothesis.

Adult↗
PubMed2006

Carisoprodol intoxications: a retrospective study of forensic autopsy material from 1992-2003.

Carisoprodol is commonly prescribed as a centrally acting muscle relaxant, but it is also subject to abuse. The literature describing fatal intoxications with the drug is limited to a relatively small number of cases, and there are inconsistencies with regard to which concentration levels that are toxic. We therefore investigated all forensic autopsies at the Norwegian Institute of Public Health during the period 1992-2003 where carisoprodol was detected. The median concentrations of carisoprodol in intoxication with carisoprodol only or with only minor other analytical findings was 36 mg/l (range 8-65 mg/l; n=5). In the rest of the intoxications, the relevance of carisoprodol relative to the other drugs detected was variable (n=93). When the number of intoxications with carisoprodol each year were divided by the number of defined daily doses (DDD) sold, a fatal toxicity index between 5.6 and 6.9 deaths/1 million DDD was obtained. The total number of cases where carisoprodol was detected increased during the period studied, which correlated to sales figures for the drug. We conclude that carisoprodol can be fatal in concentrations below those indicated in some of the previously published literature. There were, however, only a small number of cases where the cause of death can be attributed to use of carisoprodol alone.

Adolescent↗
PubMed2003

Tumor estrogen content and clinico-morphological and endocrine features of endometrial cancer.

OBJECTIVES: To compare estrogen concentrations in endometrial cancer tissue with those in macroscopically normal endometrium and with certain morphological characteristics of the tumor and endocrine parameters in patients. METHODS: The estradiol content was evaluated by radioimmunoassay after homogenization and extraction in 78 adenocarcinomas (61 from postmenopausal patients). RESULTS: Higher concentrations of estradiol in tumor tissue samples than in macroscopically normal endometrium were found in patients of both reproductive and postmenopausal age. This difference was the same in patients with either endometrial carcinoma type I or type II. No association between tumor steroid receptor levels, estradiol concentrations in blood serum, and timing of menopause with intratumoral estradiol contents was discovered. Estradiol concentrations in tumor tissues correlated positively with the clinical stage of disease and rate of tumor invasion (in patients with peripheric/lower type of fat topography), and negatively with tumor differentiation stage (in patients with central/upper type of fat topography) and the percentage of intact double-stranded DNA in normal endometrium. CONCLUSIONS: Tumor estrogen content in endometrial cancer has clinical significance that is modified in the presence of certain endocrine characteristics related to insulin resistance. The role of local estrogen production (aromatase activity) in this setting deserves special study.

Aged↗