Nomogram for the prediction of unbound phenytoin concentrations in patients on a combined treatment of phenytoin and valproic acid

The interpretation of the total phenytoin (PT) concentration can be problematic if valproic acid (VPA) is given as a comedication, because VPA displaces PT from the protein binding sites and can increase the free fraction of PT. In order to estimate the free or unbound PT concentration (PTf) from the total PT concentration (PTt) and VPA concentration, a nomogram was constructed and evaluated. Data of 84 patients on combined therapy with PT and VPA were used in drawing up the regression equation (PTf = 0.0792.PTt + 0.000636.PTt.VPA) from which the nomogram was constructed. The predictions were checked using another 33 patients whose serum concentrations were determined in the morning and in addition several times during the day. The results show that using this method the PTf concentrations can be accurately estimated from the PTt and VPA concentrations.     

Effect of ICV infusion of CRF on blood pressure and adrenal steroids in rabbits

The effect of prolonged, 22 h long, intracerebroventricular (i.c.v.) infusion of corticotropin-releasing hormone (CRF) on plasma cortisol, corticosterone and electrolyte concentrations, mean arterial blood pressure (MAP) and heart rate (HR) were investigated in conscious rabbits. During i.c.v. infusion of CRF, 1 and 3 μ/h, at a rate of 17 μl/h, plasma cortisol and corticosterone concentrations rose to the level noted after ACTH stimulation in rabbits. Plasma [Na] did not change, but plasma [K] was reduced and plasma osmolality increased during the infusion of CRF, 3 μ/h. MAP and HR, recorded continuously during i.c.v. infusion of CRF, changed only with the higher dose of CRF: MAP was elevated during the first 5 h of infusion, and then returned to the control level. HR was lower than control at the end of the first hour of infusion and again between 9 and 15 h of infusion. The prolonged rise of CRF concentration in the brain induced a sustained rise in circulating adrenal steroid hormones. MAP did not increase to the level noted after bolus i.c.v. injection of CRF and the rise in MAP was not sustained.     

Effect of Simultaneous Didanosine Administration on Itraconazole Absorption in Healthy Volunteers

Study Objective . To investigate the effect of simultaneously administered didanosine (ddI) on the absorption of a single dose of itraconazole. Design . Randomized, crossover, unblinded single-dose pharmacokinetic study in healthy volunteers. Comparisons of itraconazole alone and itraconazole with simultaneous ddI were performed on days 1 and 15. Setting . A university medical center. Patients . Seven healthy men and women. Six subjects (86%) completed the study; one was removed due to the development of a rash. Interventions . Volunteers received a single 200-mg oral dose of itraconazole or itraconazole with concomitant oral ddI 300 mg (two 150-mg tablets) dispersed in 240 ml water. Each regimen was separated by a 2-week washout period. Serum samples were obtained frequently for 12 hours after the dose. Measurements and Main Results . Concentrations of itraconazole were determined using a microbiologic assay. Individual concentrations in serum versus time data were evaluated by linear regression analysis. Peak serum concentration and time to peak were determined by visual inspection of each individual's serum concentration-time curve. A mean ± SD peak serum itraconazole concentration of 0.90 ± 0.30 μg/ml was observed at 3.0 ± 0.7 hours when itraconazole was administered alone, compared with undetectable levels in all patients during therapy with ddI. Conclusions . Simultaneous oral administration of ddI significantly decreases absorption of itraconazole. These drugs should not be administered concurrently.     

The role of the psychiatrist in the team treatment of the adult patient with burns.

Improved survival rates for patients with major burn injuries and the consistent finding of significant long-term psychologic disability among survivors of burn trauma call for a redefinition of the role of the psychiatric consultant in the care of patients with burns. In addition to the traditional functions of diagnosis and treatment of discrete psychiatric disorders in patients with burns, this expanded role includes assisting the patient's normal process of psychologic adaptation after injury, assessing and managing burn pain, and facilitating communication among all members of the burn team. The functions of the psychiatrist are most effectively carried out when the psychiatrist is able to participate on a regular basis in the care of every patient as a member of the burn team.     

The clinical course of Felty's syndrome compared to matched controls

In a cohort of 919 patients with definite or classic rheumatoid arthritis followed prospectively since 1966, we identified 36 patients with Felty's syndrome (FS). Their clinical course was compared to that of 72 matched controls from the same cohort. Patients with FS had more extraarticular features and more infections than control patients. The presence of joint erosions, serial Lansbury indices, and death rates were similar in both groups. Cardiovascular disease was the commonest cause of death in both groups, accounting for 32% of all deaths. Sepsis accounted for 10% of deaths in the group with FS and 13% of deaths in the controls.