Plasma pharmacokinetics of high-dose oral busulfan in children and adults undergoing bone marrow transplantation

Abstract: We have analyzed the plasma pharmacokinetics of busulfan in 272 patients receiving high-dose oral busulfan and intravenous cyclophosphamide in conjunction with allogeneic or autologous bone marrow transplantation. The patients ranged in age from 2 months to 59 yr (mean 10, median 12 yr) and had the following diagnoses: thalassemia or sickle cell anemia (n = 74); leukemia or myelodysplasia (n = 112); inborn errors of metabolism (n = 41) or immunodeficiency (n = 45). Plasma specimens were collected following the first dose for each patient which ranged from 1 to 4 mg/kg (mean ± SD, 1.21 ± 0.41, median 1.15). Busulfan was quantitated using ultraviolet absorbance detection after derivatization and HPLC separation. Pharmacokinetic parameters were derived by modeling the raw data to fit first-order single compartment kinetics. The kinetic parameters showed wide interpatient variability independent of age and diagnosis. There was a statistically significant correlation of age with the following parameters: area under the curve (AUC); maximal concentration; minimum concentration; clearance; volume of distribution and absorption half-time. The coefficients of determination (i.e. correlation coefficient squared) were low ranging from 0.04 to 0.12 implying only a small part (i.e. 4–12%) of the variance was explained by age. Although busulfan pharmacokinetics are age-related most of the variability is not explained by age or diagnosis.     

Persistent dizziness after surgical treatment of vertigo: an exploratory study of prognostic factors.

OBJECTIVE: Persistent vertigo and imbalance can occur after surgery for vertigo regardless of surgical approach. This study explored for factors affecting outcome of vertigo surgery. STUDY DESIGN: Patient survey and chart review. SETTING: Tertiary referral neurotologic private practice. PATIENTS/INTERVENTION: Of 111 patients (57.7% female; mean age, 52.3 yr), 59 underwent vestibular nerve section (middle fossa, retrolabyrinthine, and translabyrinthine), 25 underwent transmastoid labyrinthectomy, and 27 underwent endolymphatic sac shunt. Eighty-three percent had Ménière's disease. Mean follow-up was 4.3 years. MAIN OUTCOME MEASURES: Primary outcomes included American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) vertigo score and class, number of spells per month, current and change in AAO-HNS disability rating, vertigo and imbalance severity ratings, and frequency of imbalance. RESULTS: Three preoperative factors were consistently related to outcome: AAO-HNS disability rating, imbalance frequency rating, and duration of first symptom ([rho] = 0.19-0.51; all p's < 0.05). Greater disability and more frequent imbalance related to poorer outcome, but longer duration of disease related to better outcome. Presurgery vertigo characteristics were generally not related to outcome. Ménière's patients were more likely to have improvement in imbalance, as were those with no other significant disease and no allergy. The presence of tinnitus in the contralateral ear was associated with poorer outcomes, including a lower rate of results of Classes A and B (p = 0.023). Vertigo as a first symptom and the presence of eye disease also showed relationships to poorer outcome. CONCLUSION: Those rating themselves as more disabled before surgery are less likely to achieve the best outcomes, whereas frequency and severity of preoperative vertigo are not predictive. Several possible prognostic factors were identified that warrant future prospective study.     

Body composition and physical activity in end-stage renal disease.

OBJECTIVE: The study objective was to examine the relationship between visceral and somatic protein stores and physical activity in individuals with end-stage renal disease. DESIGN: This was a prospective single-center study. SETTING: The study took place at the Vanderbilt University Outpatient Dialysis Unit and General Clinical Research Center. PATIENTS: Fifty-five patients with prevalent chronic hemodialysis (CHD) were included: 33 males, 22 females, 45 African Americans, 9 Caucasians, and 1 Asian. The mean age was 47.0 +/- 1.6 years, height was 166.4 +/- 13.9 cm, and weight was 83.1 +/- 2.6 kg. METHODS: Body composition was measured by dual-energy x-ray absorptiometry. Minute-by-minute physical activity was assessed over a 7-day period with a triaxial accelerometer. Participants were interviewed by a trained registered dietitian for two 24-hour diet recalls (one from a hemodialysis day; one from a nonhemodialysis day). Laboratory values for serum concentrations of albumin, prealbumin, C-reactive protein, and creatinine were also collected. MAIN OUTCOME MEASURE: Predictors of somatic protein stores were the main outcome measure. RESULTS: Serum albumin was negatively and significantly correlated with the percentage of fat mass (P = .016) and kg of fat mass (P = .044). C-reactive protein was positively and significantly correlated with body weight (P = .006), percentage of fat mass (P = .017), kg of fat mass (P = .006), and body mass index (P = .004). Physical activity and total daily protein intake were the strongest predictors of the amount of lean body mass (P = .01 and .003, respectively). CONCLUSION: The association between somatic protein and visceral protein stores is weak in patients with CHD. Whereas increased levels of physical activity and total daily protein intake are associated with higher lean body mass in patients with CHD, higher adiposity is associated with higher C-reactive protein and lower albumin values.     

Nursing time to program and assess deep brain stimulators in movement disorder patients.

The use of deep brain stimulation (DBS) to treat movement disorders such as Parkinson's disease, essential tremor, and dystonia is increasing. Although some published literature describes the methods for DBS programming, the time and nursing requirements to run a DBS surgical program have not been examined previously. For this study, we prospectively recorded the time required for both assessments and programming of the DBS from the preoperative period to 1 year after surgery in a variety of patients. Results showed that the mean total time spent programming the stimulator and assessing these patients ranged from 18.0-36.2 hours per patient. It took twice as long to program the stimulator in patients with Parkinson's disease as it did in patients with essential tremor or dystonia. When setting up a program for movement disorders surgery, nursing time spent on patient assessment and programming should be considered in the workload.     

Psychological and family functioning and quality of life in adolescents with cystic fibrosis.

BACKGROUND: The life expectancy of individuals with CF has increased to 33 years. Thus, issues such as quality of life and psychological well-being, previously thought to be of lesser importance than physical well-being, are now recognised as significant factors. This study examined the interrelationships between quality of life, family functioning, individual psychopathology and optimism of adolescents with CF. METHODS: Adolescents attending the CF clinic completed a number of questionnaires. Quality of Life was measured using the Cystic Fibrosis Questionnaire, family functioning by the Family Environment Scale (3rd edition), general psychopathology with the Symptom Checklist-90-Revised and optimism for the future by the Hunter Opinions and Personal Expectations Scale. Disease severity was assessed using the Shwachman score and spirometry at the time of questionnaire completion. RESULTS: The level of psychopathology (12.5% of those 13 years and over) in the group was lower than that reported for young people in Australia (15-20%). The results indicated that young people with a delayed diagnosis and those who are alienated from their families may be in need of additional psychosocial support. The group was hopeful and positive about their future and these attributes were independent of clinical measures of disease severity. In general, these young people scored relatively highly on the quality of life scale. For example the mean standardised score for physical functioning was 70 points, for respiratory symptoms was 63 points and for emotional state was 78 points. Increased levels of psychopathology and lack of hope for the future were however associated with lower ratings on a number of quality of life measures. Family cohesiveness, expressiveness and organization were associated with better psychological functioning in the young people. CONCLUSIONS: Adolescents with CF appear to be a psychologically well functioning and well-adjusted group. These findings support the importance of a more sophisticated model of well-being for adolescents with CF, which explores the young person's views on their quality of life and wider support frameworks rather than relying solely on measures of physical health to gauge well-being.