Insight into the pathogenesis of chronic lymphocytic leukemia (CLL) through analysis of IgVH gene usage and mutation status in familial CLL

To address the proposition that familial B-cell chronic lymphocytic leukemia (CLL) may exhibit a more restricted phenotype than sporadic CLL with respect to immunoglobulin gene usage or ontogenic development, we compared immunoglobulin (Ig) heavy chain variable region (VH) gene usage and IgVH mutation status in 327 patients with CLL from 214 families with 724 patients with sporadic cases. The frequency of mutated CLL was higher in familial CLL (P < .001), and there was evidence of intrafamilial concordance in mutation status (P < .001). The repertoire and frequency of IgVH usage was, however, not significantly different between familial and sporadic CLL. Furthermore, IgVH usage was not correlated between affected members of the same family. These observations provide evidence that familial CLL is essentially indistinguishable from sporadic CLL, favoring a genetic basis to disease development in general rather than a simple environmental etiology.     

Management of acute proximal deep vein thrombosis: pharmacoeconomic evaluation of outpatient treatment with enoxaparin vs inpatient treatment with unfractionated heparin

OBJECTIVES: A landmark Canadian randomized controlled clinical trial compared treatment of acute proximal vein thrombosis via low-molecular-weight heparin (LMWH) [enoxaparin] administered primarily at home with IV unfractionated heparin (UH) in the hospital. Results demonstrated equivalent safety and efficacy for home care with enoxaparin with a reduction in cost. Our objective was to validate these findings in the routine practice setting of a US health maintenance organization. DESIGN: Retrospective analysis of medical and administrative records of health-plan members meeting inclusion-exclusion criteria of the Canadian trial during the period from 1995 to 1998. SETTING: Staff-model health maintenance organization serving New Mexico. PATIENTS:Persons presenting as outpatients from 1995 to 1996 or from 1997 to 1998 with acute, proximal deep vein thrombosis (DVT) diagnosed by duplex ultrasonography. INTERVENTIONS: Initial anticoagulant therapy of IV UH administered in the hospital (from 1995 to 1996 group, n = 64) or subcutaneous LMWH (enoxaparin) administered primarily at home (from 1997 to 1998 group, n = 65), followed by warfarin therapy. RESULTS: No statistically significant differences were observed in the number of recurrent venous thromboembolic events (p = 0.36) or bleeding events (p = 1.0). Mean +/- SD cost per patient was 9,347 dollars +/- 8,469 in the enoxaparin group compared with 11,930 dollars +/- 10,892 in the UH group, a difference of - 2,583 dollars (95% bootstrap-adjusted asymmetrical confidence interval, - 6,147 dollars, + 650 dollars). CONCLUSIONS: Retrospective replication of the Canadian study in a US routine (managed) care setting found similar clinical and economic outcomes. Treatment of acute proximal DVT with enoxaparin in a primarily outpatient setting can be accomplished safely and yields savings through avoidance or minimization of inpatient stays.     

Hand function is impaired in healthy older adults at risk of Parkinson’s disease

Abnormal substantia nigra morphology in healthy individuals, viewed with transcranial ultrasound, is a significant risk factor for Parkinson’s disease. However, little is known about the functional consequences of this abnormality (termed ‘hyperechogenicity’) on movement. The aim of the current study was to investigate hand function in healthy older adults with (SN+) and without (SN?) substantia nigra hyperechogenicity during object manipulation. We hypothesised that SN+ subjects would exhibit increased grip force and a slower rate of force application compared to SN? subjects. Twenty-six healthy older adults (8 SN+ aged 58 ± 8 years, 18 SN? aged 57 ± 6 years) were asked to grip and lift a light-weight object with the dominant hand. Horizontal grip force, vertical lift force, acceleration, and first dorsal interosseus EMG were recorded during three trials. During the first trial, SN+ subjects exhibited a longer period between grip onset and lift onset (i.e. preload duration; 0.27 ± 0.25 s) than SN? subjects (0.13 ± 0.08 s; P = 0.046). They also exerted a greater downward force prior to lift off (?0.54 ± 0.42 N vs. ?0.21 ± 0.12 N; P = 0.005) and used a greater grip force to lift the object (19.5 ± 7.0 N vs. 14.0 ± 4.3 N; P = 0.022) than SN? subjects. No between group differences were observed in subsequent trials. SN+ subjects exhibit impaired planning for manipulation of new objects. SN+ individuals over-estimate the grip force required, despite a longer contact period prior to lifting the object. The pattern of impairment observed in SN+ subjects shares similarities with de novo Parkinson’s disease patients.     

Perceived drinking norms among black college students: The race of reference group members

Social norms have been consistently shown to influence alcohol use among college students. Much of the research in this area is focused on mostly White samples. This study sought to expand our understanding of social norms theory by examining perceptions of normative alcohol use among Black students and determining the impact of the race of reference group members on personal alcohol use. Participants (N = 130; 73.8% female) completed an online questionnaire. Results of repeated measures of analysis of variance indicated that participants perceived all referent groups (i.e., White, same race, typical student) as drinking significantly more than they did. Results of hierarchical regression analysis indicated that perceptions of typical student drinking significantly predicted personal alcohol use. Implications for practice and research are discussed.