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.     

Finding temporary relief: strategy for nursing recruitment in northern aboriginal communities.

To address a recurring shortage of nurses in the aboriginal communities of Northwestern Ontario, the First Nations and Inuit Health Branch, Health Canada, commissioned a study to explore the viability of establishing a relief pool among nurses from nearby small industrial towns. An open/close-ended survey completed by a random sample of 237 nurses from the target population documented levels of awareness, willingness, and preparedness for northern practice, as well as recruitment incentives and disincentives. Findings demonstrate an awareness of the overlap between the professional and personal dimensions characteristic of such practices, and suggest support for innovative rotations that would cut across federal/provincial/community jurisdictions. Although complex, given time and willingness, a regional relief system seems viable.     

A case-controlled study of altered visual art production in Alzheimer's and FTLD.

OBJECTIVE: To characterize dementia-induced changes in visual art production. BACKGROUND: Although case studies show altered visual artistic production in some patients with neurodegenerative disease, no case-controlled studies have quantified this phenomenon across groups of patients. METHOD: Forty-nine subjects [18 Alzheimer disease, 9 frontotemporal dementia (FTD), 9 semantic dementia (SD), 15 healthy older controls (NC)] underwent formal neuropsychologic testing of visuospatial, perceptual, and creative functioning, and produced 4 drawings. Subjective elements of drawings were rated by an expert panel that was blind to diagnosis. RESULTS: Despite equal performance on standard visuospatial tests, dementia groups produced distinct patterns of artistic features that were significantly different from NCs. FTDs used more disordered composition and less active mark-making (P<0.05). Both FTDs and SDs drawings were rated as more bizarre and demonstrated more facial distortion than NCs (P<0.05). Also, SDs drastically failed a standardized test of divergent creativity. Alzheimer disease artwork was more similar to controls than to FTDs or SDs, but showed a more muted color palette (P<0.05) and trends toward including fewer details, less ordered compositions, and occasional facial distortion. CONCLUSIONS: These group differences in artistic style likely resulted from disease-specific focal neurodegeneration, and elucidate the contributions of particular brain regions to the production of visual art.     

Bone marrow fat content in relation to bone remodeling and serum chemistry in intact and ovariectomized dogs

Summary It was previously shown that 11 months after ovariectomy the volume fraction of trabecular bone in the spine and 11th rib medullary canal of Beagle dogs (6 control, 9 ovariectomized) was significantly reduced. In this paper it is shown that these changes are accompanied by increased marrow fat volume in the 11th rib (59.0±9.5% vs. 44.3 ±10.0%). Conversely, the volume fraction of functional (hematopoietic) cells in the marrow was reduced by ovariectomy. Additionally, variations in marrow fat volume were tested for correlation with 22 other variables pertinent to bone physiology. Marrow fat volume was significantly positively correlated with serum osteocalcin, rib trabecular bone porosity, rib cross-sectional area, and gains in body weight. It was negatively correlated with serum estrogen concentrations and the extent of rib trabecular surfaces labeled with tetracycline.     

Ruvalcaba-Myhre-Smith Syndrome

In 1980 a syndrome was first described in two adult males, consisting of macrocephaly, pigmented macules on the glans and shaft of the penis, and hamartomatous intestinal polyps. Since then, 10 additional cases have been identified. Herein, we present two new cases and review the cutaneous manifestations as well as additional features in patients with the Ruvalcaba-Myhre-Smith syndrome.     

The “Demon Plague” and Access to Care Among Asian Undocumented Immigrants Living with HIV Disease in New York City

Access to and utilization of care for HIV-positive Asians (A) and Pacific Islanders (PI) have been largely unaddressed despite the rising influx of immigrants from Asia and the Pacific to the United States and the growing HIV prevalence in these regions. This paper describes the cultural attitudes, behaviors, and perceptions that affect access to and utilization of care among Asian undocumented noncitizens living with HIV/AIDS (UNWHA) in New York City. Sixteen semistructured interviews with HIV-positive UNWHAs revealed that their access to care was influenced by community misperceptions of HIV transmission, discriminatory attitudes towards persons living with HIV, competing immigration related stressors, and difficulty navigating service systems. These findings underscore the importance of integrating HIV treatment with primary prevention and awareness of immigration-related stressors to ensure timely access to screening services and care among Asian UNWHAs.