DJ-1( PARK7), a novel gene for autosomal recessive, early onset parkinsonism

Abstract. Four chromosomal loci (PARK2, PARK6, PARK7, and PARK9) associated with autosomal recessive, early onset parkinsonism are known. We mapped the PARK7 locus to chromosome 1p36 in a large family from a genetically isolated population in the Netherlands, and confirmed this linkage in an Italian family. By positional cloning within the refined PARK7 critical region we recently identified mutations in the DJ-1 gene in the two PARK7-linked families. The function of DJ-1 remains largely unknown, but evidence from genetic studies on the yeast DJ-1 homologue, and biochemical studies in murine and human cell lines, suggests a role for DJ-1 as an antioxidant and/or a molecular chaperone. Elucidating the role of DJ-1 will lead to a better understanding of the pathogenesis of DJ-1-related and common forms of Parkinsons disease.     

Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the prospective LNH87-2 protocol--a groupe d'Etude des lymphomes de l'Adulte study.

PURPOSE: To present the final analysis, with a median follow-up of 8 years, of the LNH87-2 randomized study, which compares consolidative sequential chemotherapy (ifosfamide plus etoposide, asparaginase, and cytarabine) with high-dose therapy (HDT) using cyclophosphamide, carmustine, and etoposide (CBV regimen) followed by stem-cell transplantation in patients with aggressive non-Hodgkin's lymphoma in first complete remission after induction, focusing on high/intermediate- and high-risk patients identified by the age-adjusted international prognostic index. PATIENTS AND METHODS: Among the 916 eligible patients, 451 presented with two (n = 318) or three (n = 133) risk factors. After reaching complete remission to induction therapy, 236 of these higher risk patients were assessable for the consolidation phase, with 125 patients in the HDT arm and 111 in the sequential chemotherapy arm. RESULTS: Among these 451 higher risk patients, 277 (61%) achieved complete remission after induction treatment. In the population of 236 randomized patients, HDT was superior to sequential chemotherapy, with 8-year disease-free survival rates of 55% (95% confidence interval [CI], 46% to 64%) and 39% (95% CI, 30% to 48%), respectively (P =.02; relative risk, 1.56). The 8-year survival rate was significantly superior in the HDT arm (64%; 95% CI, 55% to 73%) compared with the sequential chemotherapy arm (49%; 95% CI, 39% to 59%) (P =.04; relative risk, 1.51). CONCLUSION: On the basis of the final analysis of this prospectively treated series of patients, retrospectively analyzed on the basis of the International Prognostic Index, we hypothesize that HDT benefits patients at higher risk who achieve complete remission after induction treatment.     

The aging slow wave: a shifting amalgam of distinct slow wave and spindle coupling subtypes define slow wave sleep across the human lifespan

Study ObjectivesSlow wave and spindle coupling supports memory consolidation, and loss of coupling is linked with cognitive decline and neurodegeneration. Coupling is proposed to be a possible biomarker of neurological disease, yet little is known about the different subtypes of coupling that normally occur throughout human development and aging. Here we identify distinct subtypes of spindles within slow wave upstates and describe their relationships with sleep stage across the human lifespan.MethodsCoupling within a cross-sectional cohort of 582 subjects was quantified from stages N2 and N3 sleep across ages 6–88 years old. Results were analyzed across the study population via mixed model regression. Within a subset of subjects, we further utilized coupling to identify discrete subtypes of slow waves by their coupled spindles.ResultsTwo different subtypes of spindles were identified during the upstates of (distinct) slow waves: an “early-fast” spindle, more common in stage N2 sleep, and a “late-fast” spindle, more common in stage N3. We further found stages N2 and N3 sleep contain a mixture of discrete subtypes of slow waves, each identified by their unique coupled-spindle timing and frequency. The relative contribution of coupling subtypes shifts across the human lifespan, and a deeper sleep phenotype prevails with increasing age.ConclusionsDistinct subtypes of slow waves and coupled spindles form the composite of slow wave sleep. Our findings support a model of sleep-dependent synaptic regulation via discrete slow wave/spindle coupling subtypes and advance a conceptual framework for the development of coupling-based biomarkers in age-associated neurological disease.     

Adaptive black blood fast spin echo for end‐systolic rest cardiac imaging

Black Blood Fast Spin Echo imaging of the heart is usually performed during mid‐diastolic rest. This is a direct consequence of the long inversion time required to suppress the blood signal, which is constrained by the T₁ of the blood, and of the heart rate. To overcome these constraints, and to acquire black blood images in the end‐systolic rest period, a new approach is introduced aiming at adaptively predicting the best time to prepare and acquire MR signals. It is based on a RR interval prediction algorithm and on a cardiac cycle model. The proposed method was applied to 14 healthy volunteers and is compared to a simple alternative method using a fixed delay and to the standard black blood imaging method for imaging in the mid‐diastolic rest period. Results show that the proposed method offers an increased robustness in terms of trigger delay error and image quality compared to the tested simple alternative. Also, it has been shown by qualitative analysis done by an experienced observer that the right ventricle, especially the thin right ventricle free wall, is better depicted with our method than with the standard mid‐diastolic rest acquisition. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Serum cystatin C is not a better marker of creatinine or digoxin clearance than serum creatinine

AIMS: To assess whether cystatin C, a new serum marker of renal function, is a better index of creatinine or digoxin clearance than serum creatinine in older people. METHODS: Twenty-two volunteers over the age of 65 years (mean 73 +/- 5) were recruited from a healthy elderly volunteer database. None of the volunteers was taking digoxin or other medication known to interfere with digoxin kinetics or assay. Digoxin was infused at a dose of 7-10 microg kg(-1) and blood samples were taken over the following 48 h and assayed for serum digoxin. Serum cystatin C, creatinine and creatinine clearance were measured and a calculated creatinine clearance was estimated using the Cockcroft Gault formula. Digoxin clearance was calculated using a pharmacokinetic software package. All values were log transformed to normalize their distribution. RESULTS: Of the 22 volunteers enrolled into the study, 18 completed the study. Serum cystatin C ranged between 0.72 and 1.89 mg l(-1) and serum creatinine ranged from 69.6 to 153.9 micromol l(-1). Measured creatinine clearance ranged from 38 to 123 ml min(-1) and calculated creatinine clearance from 29.5 to 88.0 ml min(-1). Digoxin clearance ranged from 51.0 to 103.5 ml min(-1). Cystatin C correlated extremely well with creatinine (r=0.93, P<0.001, 95% CI 0.82, 0.97) and with creatinine clearance (r=0.67, P=0.002, 95% CI 0.3, 0.87). Neither serum cystatin C nor serum creatinine correlated with digoxin clearance (r=0.25, P=0.31, 95% CI -0.25, 0.64 and r=0.44, P=0.068, 95% CI -0.03, 0.75, respectively). Measured creatinine clearance, however, did correlate well with digoxin clearance (r=0.55, P=0.018, 95% CI 0.11, 0.81). CONCLUSIONS: Serum cystatin C and serum creatinine show very similar correlations with creatinine and digoxin clearances. Serum cystatin C does not offer any advantages in this respect. It remains to be seen whether cystatin C offers any advantage over creatinine in elderly people in other respects.     

Chagas disease and globalization of the Amazon

The increasing number of autochthonous cases of Chagas disease in the Amazon since the 1970s has led to fear that the disease may become a new public health problem in the region. This transformation in the disease's epidemiological pattern in the Amazon can be explained by environmental and social changes in the last 30 years. The current article draws on the sociological theory of perverse effects to explain these changes as the unwanted result of the shift from the "inward" development model prevailing until the 1970s to the "outward" model that we know as globalization, oriented by industrial forces and international trade. The current article highlights the implementation of five new patterns in agriculture, cattle-raising, mining, lumbering, and urban occupation that have generated changes in the environment and the traditional indigenous habitat and have led to migratory flows, deforestation, sedentary living, the presence of domestic animals, and changes in the habitat that facilitate colonization of human dwellings by vectors and the domestic and work-related transmission of the disease. The expansion of Chagas disease is thus a perverse effect of the globalization process in the Amazon.