Reduced parenchymal cerebral blood flow is associated with greater progression of brain atrophy: The SMART-MR study

Global cerebral hypoperfusion may be involved in the aetiology of brain atrophy; however, long-term longitudinal studies on this relationship are lacking. We examined whether reduced cerebral blood flow was associated with greater progression of brain atrophy. Data of 1165 patients (61 ± 10 years) from the SMART-MR study, a prospective cohort study of patients with arterial disease, were used of whom 689 participated after 4 years and 297 again after 12 years. Attrition was substantial. Total brain volume and total cerebral blood flow were obtained from magnetic resonance imaging scans and expressed as brain parenchymal fraction (BPF) and parenchymal cerebral blood flow (pCBF). Mean decrease in BPF per year was 0.22% total intracranial volume (95% CI: –0.23 to –0.21). Mean decrease in pCBF per year was 0.24 ml/min per 100 ml brain volume (95% CI: –0.29 to –0.20). Using linear mixed models, lower pCBF at baseline was associated with a greater decrease in BPF over time (p = 0.01). Lower baseline BPF, however, was not associated with a greater decrease in pCBF (p = 0.43). These findings indicate that reduced cerebral blood flow is associated with greater progression of brain atrophy and provide further support for a role of cerebral blood flow in the process of neurodegeneration.     

Correction to: Working Overtime: Altered Functional Connectivity in Working Memory Following Regular Cannabis Use in Young Adults

International Journal of Mental Health and Addiction - The caption for Fig. 1 was incorrect in this article as originally published.     

Fc gamma receptor II (CD32) on malignant B cells influences modulation induced by anti-CD19 monoclonal antibody

Antigenic modulation is one of many factors determining the effectiveness of monoclonal antibody (MoAb)-mediated therapy. To select the isotype of a CD19 MoAb most suitable for radioimmunotherapy of patients with B-cell malignancies, we studied the influence of MoAb isotype on modulation, after binding of the MoAb to different cell-line cells. The CD19-IgG1 MoAb was found to induce modulation of CD19 antigens on Daudi cell line cells more rapidly than did its IgG2a switch variant. We provide evidence that this difference in modulation rate is caused by the expression of Fc gamma receptor II (Fc gamma RII) on these cells. Experiments aimed at elucidating the mechanism of Fc gamma RII involvement in modulation induction by CD19-IgG1 showed that Fc gamma RII did not comodulate with CD19 MoAbs. However, cocrosslinking of CD19 and Fc gamma RII with CD19-IgG1 MoAb resulted in enhanced calcium mobilization in Daudi cells. This increased signal induction accompanies the enhanced capping and subsequent modulation of CD19 antigens. Because Fc gamma RII is expressed in varying densities on malignant B cells in all differentiation stages, our results have implications for the MoAb isotype most suitable for use in MoAb-based therapy of patients with B-cell malignancies.     

A radioreceptor assay for quantitating plasma factor VIII/von Willebrand's protein

A sensitive and precise radioreceptor assay for determining plasma levels of human factor VIII/von Willebrand's factor (FVIII/vWF) has been developed by taking advantage of the FVIII/vWF receptor sites on human platelets. Paraformaldehyde-fixed platelets, which were processed and then stored, retained FVIII/vWF binding activity and therefore could be used as a convenient source of receptors. The human plasma samples to be tested were initially filtered on 4% agarose columns to concentrate the FVIII/vWF protein in the void volume and to remove the factor(s) that interferes with the assay. The percent recovery of FVIII/vWF in the pooled eluent was measured by the recovery of added trace 125I-FVIII/vWF. The coefficients of intra- and interassay variation were 6% and 10%, respectively. The plasma FVIII/vWF concentrations determined by the assay for pooled normal plasma, hemophilia A plasma, and plasmas from two patients with von Willebrand's disease were 16.3 +/- 0.5, 52.6 +/- 1.5, 6.8 +/- 0.8, and 3.2 +/- 0.2 microgram/ml, respectively. The range of plasma FVIII/vWF concentrations varied between 8.3 microgram/ml and 24.9 microgram/ml for 10 normal adults. The plasma FVIII/vWF concentrations determined by the radioreceptor assay correlated well with levels measured by the ristocetin-induced platelet aggregation method, thus demonstrating the functional relevancy of the radioreceptor assay for plasma FVIII/vWF.     

Role of cholecystokinin in the regulation of liquid gastric emptying and gastric motility in humans: studies with the CCK antagonist loxiglumide

Background—Exogenous cholecystokinin (CCK)inhibits antral motility and slows gastric emptying (GE) but the effectof endogenous CCK on the gastric motor mechanisms responsible for GEremains unclear.
Methods—The effect of the CCK-A antagonistloxiglumide (LOX) on GE and motility was studied using magneticresonance imaging in six healthy volunteers after ingestion of 500 mlIntralipid 10% (550 kcal). Subjects were studied in the supineposition on two occasions during intravenous infusion of LOX(66 µmol/kg/h for 10 min followed by 22 µmol/kg/h) or placebo. GEwas determined every 15 minutes using transaxial abdominal scans andmotility was studied by means of 120 coronal scans, 1.2 seconds apart. For each coronal image the proximal and distal (antral) diameters weremeasured at a fixed point in the stomach to determine contraction frequency (ACF) and amplitude (AMP).
Results—GE was faster during LOX infusion thanplacebo (t_1/2 31 (22) versus 115 (67) minutes, p<0.03).There was little variation in the diameter of the proximal stomach witheither LOX or placebo. In the distal stomach marked contractileactivity was observed during LOX (ACF 2.9 (0.2) versus 1.5 (2.9) duringplacebo, p<0.01). AMP also increased during LOX compared with placebo(56 (22)% versus 27 (16)%, p<0.001).
Conclusion—The increases in antral motility arelikely to contribute to the acceleration of GE and suggest that CCK mayregulate GE by acting on the distal stomach although an effect on theproximal stomach cannot be excluded.

Keywords:loxiglumide; magnetic resonance imaging; gastricemptying; gastric motility; antral contraction

     

Relationship between lung function and physical performance in disabled older women

BACKGROUND: Understanding the association between lung function and physical performance in disabled older women helps in determining the potential for prevention and treatment strategies to decrease disability. The aim of this study was to determine the association of lung function with objective and self-reported physical performance in community-dwelling disabled older women. METHODS: The Women's Health and Aging Study I consists of 1002 disabled community-dwelling women aged > or = 65. Of these women, 840 underwent spirometry with determination of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Cross-sectional analyses included multivariate linear regression to assess the association between FEV1, FVC, FEV1/FVC, and the time to walk four meters after adjusting for confounders, including age, race, geriatric depression scale score, body mass index, muscle strength, osteoarthritis, smoking status, and cardiovascular disease. Multiple logistic regression was used to assess the association between FEV1, FVC, FEV1/FVC, and self-reported disability in physical performance. RESULTS: FEV1 was independently associated with time to walk 4 meters. For every 100 ml decrease in FEV1, there was a 0.15-second (95% confidence interval: 0.24 to 0.06) increase in time to walk 4 meters. There was an 8% increase in the prevalent odds of self-reported disability in physical performance for every 100 ml decrease in FEV1. FVC was also associated with physical performance measures. In contrast, FEV1/FVC was associated with objective but not subjective physical performance. CONCLUSION: Decreasing lung function is independently associated with decrements in objective and self-reported physical performance in disabled older women.