RESUMEN
Lifibrol is a powerful cholesterol-lowering drug of unknown mechanism of action. This investigation was carried out to determine whether the major action of lifibrol is to enhance clearance of low density lipoproteins (LDL) through the LDL-receptor pathway, and if so, whether the drug exerts its action by altering the excretion of bile acids (acidic steroids), the absorption of cholesterol, or the synthesis of cholesterol. In a first study, in two patients with complete absence of LDL receptors, lifibrol therapy had essentially no effect on plasma LDL concentrations; in two others who had a marked reduction in LDL-receptor activity, response to the drug was attenuated. These findings suggest that lifibrol requires an intact LDL-receptor pathway to exert its action. In a second study, in patients with primary moderate hypercholesterolemia, isotope kinetic studies showed that lifibrol enhanced the fractional catabolic rate of LDL-apolipoprotein B (apo B), but had no effect on transport rates of LDL; these observations likewise support the probability that lifibrol acts mainly to increase the activity of the LDL-receptor pathway. However, in a third study in hypercholesterolemic patients, lifibrol therapy failed to increase acidic steroid excretion, inhibit cholesterol absorption, or reduce net cholesterol balance. Furthermore, lifibrol treatment did not significantly reduce urinary excretion of mevalonic acid. In contrast, in a parallel study, simvastatin therapy, which is known to inhibit cholesterol synthesis, gave the expected decrease in net cholesterol balance and reduction in urinary excretion of mevalonic acid. Thus, lifibrol, like statins, appears to increase the activity of LDL receptors; but in contrast to findings with statins, it was not possible to detect a significant decreased synthesis of cholesterol, either from balance studies or from urinary excretion of mevalonic acid. This finding raises the possibility that lifibrol activates the LDL-receptor pathway through a different mechanisms which remains to be determined.
Asunto(s)
Butanoles/farmacología , Colesterol/sangre , Hidroxibenzoatos/farmacología , Hipercolesterolemia/tratamiento farmacológico , Hipercolesterolemia/metabolismo , Hipolipemiantes/farmacología , Simvastatina/farmacología , Adolescente , Adulto , Anciano , Anticolesterolemiantes/farmacología , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Hipercolesterolemia/sangre , Hipercolesterolemia/orina , Masculino , Ácido Mevalónico/orina , Persona de Mediana Edad , Método Simple Ciego , Triglicéridos/sangreRESUMEN
Conventional "staging " of traumatic brain injury (TBI) typically uses depth of coma assessed by the Glasgow Coma Scale (GCS) score near admission as a severity marker. Frequently, early GCS scores are contaminated by alcohol or drug ingestion and other, nonneurological organ system trauma. As well, this measure's usefulness is limited due to its restricted range in survivors. Here we explore the utility of using length of posttraumatic amnesia, coma duration, and age as indirect markers of severity. Cluster analytic techniques were used to examine the relationship of severity so defined to long-term outcome in 106 mild, moderate, and severe TBI patients. Results indicate complex relationships between cluster groups with the influence of age of patient being highlighted as an important moderator in determining severity of injury and later psychosocial outcome.
RESUMEN
Central nervous system (CNS) trauma can produce a multitude of physical and psychological sequelae, depending on the neurological level of injury. Clinicians have long recognized the adjustment difficulties posed in marriages of CNS trauma victims, yet there is little research documentation for this observation. The marital relationships of moderate (n = 31) and severe (n = 17) head injury (HI) groups and a spinal cord injury (SCI) group (n = 24) were assessed through spouses' self-reports in interview and through standardized questionnaires. Analyses indicated that the three groups were not statistically different in age, number of months post-injury, pre- and post-injury occupational status, and level of income. In the post-injury marital relationship, the severe HI group was significantly lower than the moderate HI and SCI groups on standardized and validated scales assessing affectional expression (p less than 0.002), dyadic satisfaction (p less than 0.001), dyadic cohesion (p less than 0.01), and total dyadic adjustment (p less than 0.001). On a scale of social role functioning, the severe HI group's performance was significantly lower than the moderate HI and SCI groups (p less than 0.005). These results empirically substantiate the clinical observation that adjustment difficulties may be more intense for wives of the severely head injured than the moderately injured or the SCI, as they must deal with neuropsychological as well as physical fall-out from the injury.