Normal cerebral perfusion measurements using arterial spin labeling: reproducibility, stability, and age and gender effects.

Before meaningful conclusions can be drawn from clinical measures of cerebral blood perfusion, the precision of the measurement must be determined and set in the context of inter- and intrasubject sources of variability. This work establishes the reproducibility of perfusion measurements using the noninvasive MRI technique of continuous arterial spin labeling (CASL). Perfusion was measured in 34 healthy normal subjects. Intersubject variability was assessed, and age and gender contributions were estimated. Intersubject variation was found to be large, with up to 100% perfusion difference for subjects of the same age and gender. Repeated measurements in one subject showed that perfusion remains remarkably stable in the short term when compared with intersubject variation and the large capacity for perfusion change in the brain. A significant decrease in the ratio of gray-matter to white-matter perfusion was found with increasing age (0.79% per year (P < 0.0005)). This appears to be due mainly to a reduction in gray-matter perfusion, which was found to decrease by 0.45% per year (P = 0.04). Regional analysis suggested that the gray-matter age-related changes were predominantly localized in the frontal cortex. Whole-brain perfusion was 13% higher (P = 0.02) in females compared to males.     

Sphingolipid metabolites in neural signalling and function

Sphingolipid metabolites, such as ceramide, sphingosine, sphingosine-1-phosphate (S1P) and complex sphingolipids (gangliosides), are recognized as molecules capable of regulating a variety of cellular processes. The role of sphingolipid metabolites has been studied mainly in non-neuronal tissues. These studies have underscored their importance as signals transducers, involved in control of proliferation, survival, differentiation and apoptosis. In this review, we will focus on studies performed over the last years in the nervous system, discussing the recent developments and the current perspectives in sphingolipid metabolism and functions.     

Liver transplant and hepatitis C in methadone maintenance therapy: a case report

Methadone maintenance therapy for the treatment of opioid dependence continues to carry a social stigma. Until recently, patients on methadone were not considered for liver transplantation. We describe the first case of a patient on methadone who received a liver transplant for end stage liver disease and was successfully treated for recurrent hepatitis C. More than five years post transplant and three years post viral clearance, the patient continues to do well and is stable on low-dose methadone. This case emphasizes the need to reconsider the non-evidence based policy adopted by transplant centers that require methadone maintenance therapy patients to stop methadone prior to consideration for transplant evaluation.     

Public health laws and implications for a national accreditation program: parallel roadways without intersection?

Public health law has been one of the leading contributors to the extension of life expectancy in the 20th century. Nonetheless, the legal infrastructure supporting public health law in the United States is underdeveloped and nonuniform. With national interest growing in public health agency accreditation, the individual legal approach taken by states may pose an obstacle to wholesale adoption of a proposed voluntary national model. This article describes the legal foundations supporting accreditation or assessment programs in states participating in the Multi-State Learning Collaborative, a project funded by the Robert Wood Johnson Foundation. The Turning Point Model State Public Health Act is recommended as one option to resolve the current impasse, assist in acceptance of a national accreditation model, and provide a common public health legal infrastructure.     

‘Translation is not enough’: using the Global Person Generated Index (GPGI) to assess individual quality of life in Bangladesh,Thailand, and Ethiopia

Currently few subjective measures of Quality of Life (QoL) are available for use in developing countries, which limits their theoretical, methodological, and practical contribution (for example, exploring the relationship between economic development and QoL, and ensuring effective and equitable service provision). One reason for this is the difficulty of ensuring that translated measures preserve conceptual, item, semantic, operational, measurement; and functional equivalence (Herdman, M., Fox-Rushby, J., & Badia, X. (1998). Quality of Life Research, 7, 331), which is illustrated by an account of the translation, pre-piloting, and administration of a new individualised QoL measure, the Global Person Generated Index or 'GPGI'. The GPGI is based on the widely used Patient Generated Index (Ruta, Camfield, & Martin, (2004) Quality of Life Research, 13, 1545.) and offers many of the advantages of the participatory approaches commonly used in developing countries, with added methodological rigour, and quantitative outcomes. It was successfully validated in Bangladesh, Thailand, and Ethiopia, using quantitative and qualitative methods--open-ended, semi-structured interviews (SSIs), conducted immediately post-administration. Both the measure and method of 'qualitative validation' described later in the paper offer an exciting alternative for future researchers and practitioners in this field. The quantitative results suggest the GPGI shows cultural sensitivity, and is able to capture both the areas that are important to respondents, and aspects of life one would expect to impact on QoL in developing countries. There were strong correlation between scores from the GPGI and SSIs for the area of health, and moderate correlations for 'material wellbeing' (MWB)('Material wellbeing' refers to respondents' perceptions of their achievement in the areas of farming, debt reduction, assets, crops, livestock, job, land, property, and agriculture) and children. Weak to moderate correlations were observed between the Satisfaction with Life Scale and the GPGI; however, the highest coefficient was between the GPGI and the most conceptually similar item. Statistically significant differences were seen in GPGI scores between rich and poor, urban and rural respondents, and different countries. Health and material wellbeing scores, derived from the SSIs, also showed a linear relationship with GPGI scores, with a suggestion of curvilinearity at the higher levels, as predicted by a general QoL causal model. In conclusion, the GPGI has great potential for use in this area, especially when supported by extensive interviewer training, and supplemented with a cognitive appraisal schedule.     

Characterization of the Medical Symptom Validity Test in evaluation of clinically referred memory disorders clinic patients.

We prospectively evaluated performance of 63 referrals to a memory disorders clinic who received the Medical Symptom Validity Test (MSVT) as part of their standard neuropsychological evaluation. The patients were grouped based on independent medical diagnoses and presence or absence of a potential financial incentive to under-perform. Twenty-seven patients (42.9%) scored below cutoffs on the MSVT symptom validity indices. Two individuals in the potential financial incentive group showed clear signs of invalid responding (18.2%). Twenty-two of the remaining 25 patients who failed the symptom validity indices corresponded to the dementia profile. Three individuals did not correspond to the dementia profile but are thought to have performed validly representing a 4.8% false positive rate. When considering all MSVT indices, the base rate of invalid responding in the potential financial incentive to under-perform group increased to 27.3%. Combining all groups our base rate of invalid responding was 4.8%. Specific performances are presented.     

Neuropsychological assessment, neuroimaging, and neuropsychiatric evaluation in pediatric and adult patients with sickle cell disease (SCD)

Traditionally, neuropsychological deficits due to Sickle Cell Disease (SCD) have been understudied in adults. We have begun to suspect, however, that symptomatic and asymptomatic Cerebrovascular Events (CVE) may account for an alarming number of deficits in this population. In the current brief review, we critically evaluated the pediatric and adult literatures on the neurocognitive effects of SCD. We highlighted the studies that have been published on this topic and posit that early detection of CVE via neurocognitive testing, neuropsychiatric evaluations, and neuroimaging may significantly reduce adult cognitive and functional morbidities.     

Cognitive and neuroimaging predictors of instrumental activities of daily living.

Impaired ability to conduct daily activities is a diagnostic criterion for dementia and a determinant of healthcare services utilization and caregiver burden. What predicts decline in instrumental activities of daily living (IADLs) is not well understood. This study examined measures of episodic memory, executive function, and MRI brain volumes in relation to baseline IADLs and as predictors of rate of IADL change. Participants were 124 elderly persons with cognitive function between normal and moderate dementia both with and without significant small vessel cerebrovascular disease. Random effects modeling showed that baseline memory and executive function (EXEC) were associated with baseline IADL scores, but only EXEC was independently associated with rate of change in IADLs. Whereas hippocampal and cortical gray matter volumes were significantly associated with baseline IADL scores, only hippocampal volume was associated with IADL change. In a model including cognitive and neuroimaging predictors, only EXEC independently predicted rate of decline in IADL scores. These findings indicate that greater executive dysfunction at initial assessment is associated with more rapid decline in IADLs. Perhaps executive function is particularly important with respect to maintaining IADLs. Alternatively, executive dysfunction may be a sentinel event indicating widespread cortical involvement and poor prognosis.